Best Practice & Research Clinical Obstetrics & Gynaecology

Progesterone and endometrial cancer

It is well established that unopposed estrogen, either endogenous or therapeutic, can induce endometrial hyperplasia and potentially endometrial cancer (EC). Anovulatory cycles, obesity, and insulin resistance are major risk factors for EC. Progestogen (progesterone and progestin), including levonorgestrel intrauterine device, are able to prevent or to treat hyperplasia, atypical hyperplasia, and even well-differentiated EC, as presented in this review. During menopausal hormone therapy, progestogens protect the endometrium against the proliferative effects of estrogens in women with a uterus. Whereas, recent epidemiologic data suggest that micronized progesterone (MP) is apparently safer for the breast, it could be less efficient than synthetic progestin on the endometrium. However, several studies from biopsies during treatment with MP do not show any increased risk of hyperplasia. Lack of compliance could explain the results on EC.

Current and future approaches to screening for endometrial cancer

Due largely to the rise in obesity and prolonged life expectancy, endometrial cancer (EC) rates have increased by 56% since the early 90s. Women at high risk (Lynch Syndrome) have a 12-47% lifetime risk of developing EC and professional societies recommend annual surveillance using transvaginal ultrasound (TVS) and endometrial biopsy (outpatients hysteroscopy) from the age of 30-35 years with hysterectomy from the age of 40 years. In women at low risk, screening is not currently advocated. The emerging data from Genome Wide Association studies (GWAS) in combination with epidemiological data may refine risk stratification in the future. In addition to screening, preventative approaches such as intrauterine progesterone may help reduce disease burden in those identified at 'higher risk'.

Endometrial cancer prevention in high-risk women

Endometrial cancer (EC) is the most common gynaecological malignancy, and its incidence is rising alongside the growing prevalence of obesity. Effective risk-reducing interventions hijacking the key mechanisms driving endometrial carcinogenesis may affect EC diagnoses if aimed at those at greatest risk. An understanding of the key risk factors and their role in tumourigenesis is critical in developing such prevention strategies. In this review, we summarise the major risk factors for EC and the evidence for available risk-reducing interventions in high-risk women. We suggest potential prevention strategies and make a case for the need for risk prediction models that identify specific groups of women at a particularly high risk of EC for whom risk-reducing interventions are likely to have a significant impact.

Establishing ovarian toxicity assessment in oncology trials

Robotic para-aortic sentinel lymph node mapping in endometrial, cervical, and ovarian cancer

The concept of pelvic sentinel lymph node mapping has been well-investigated in endometrial and cervical cancer. A variety of tracers have been used including blue dye, technetium-99-m (Tc-99 m), and fluorescent tracer indocyanine green. Pelvic sentinel lymph node mapping has shown its safety, efficacy, and diagnostic accuracy, with high sensitivity and negative predictive value of more than 90%, in retrospective cohort studies as well as in prospective trials for robotic surgery. The concept of pelvic sentinel lymph node biopsy has been incorporated in several international guidelines in early-stage endometrial cancer and a subgroup of early-stage cervical cancer, although survival data are still needed to confirm its standard use. The application of para-aortic sentinel lymph node mapping is still in a development phase, but its detection rate and diagnostic accuracy seem to be promising in initial studies. Here, an overview is given of the recent developments in the different methodologies used for identifying para-aortic sentinel lymph nodes in endometrial, cervical, and ovarian cancer.

Robot-assisted laparoscopic myomectomy: Technique & brief literature review

The worldwide growth of robot-assisted laparoscopic surgery has been exponential since its FDA approval for use in gynecologic surgery in the spring of 2005. This growth has spanned the entire gamut of gynecologic procedures and pathology. One area that has leveraged the unique aspects of robotics has been its application to the conservative surgical management of uterine fibroids. This manuscript will review the surgical technique and highlight the current situation regarding the scientific literature with an evidence-based focus on the role of robot-assisted laparoscopic myomectomy (RALM) with the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA).

Cancer genetics and breast cancer

The risk of developing breast cancer is multifactorial and, at times, modifiable. However, the risk imposed by family history and hereditary pathogenic variants in a person's genetic code is, at present, an important fixed variable. Therefore, it is imperative to identify patients at risk for hereditary breast cancer and to understand the current evidence-based approach to the management of that risk. This chapter focuses on how genes play a role in breast cancer risk, why certain genes are commonly involved in hereditary breast cancer, and what are the specific genes and genetic syndromes that put patients at risk for breast cancer. Hereditary cancer susceptibility syndromes, including Hereditary Breast and Ovarian Cancer Syndrome (HBOC - BRCA1/2), Cowden Syndrome (CS - PTEN), Li-Fraumeni Syndrome (LFS - TP53), Peutz-Jegher Syndrome (PJS - STK11), Neurofibromatosis Type 1 (NF1), and Diffuse Hereditary Gastric Cancer Syndrome (CDH1) will be discussed along with individual genes not associated with a particular syndrome (ATM, BARD1, CHEK2, and PALB2).

Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer

The long-term survival of advanced-stage ovarian cancer patients remains poor, despite extensive cytoreductive surgery, chemotherapy, and the recent addition of poly (ADP-ribose) polymerase inhibitors (PARPi). Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefit by specifically targeting peritoneal metastases, the primary site of disease recurrence. Different aspects of how HIPEC exerts its effect remain poorly understood. Improved understanding of the effects of hyperthermia on ovarian cancer cells, the synergy of hyperthermia with intraperitoneal chemotherapy, and the pharmacological and pharmacokinetic properties of intraperitoneally administered cisplatin may help identify ways to optimize the efficacy of HIPEC. This review provides an overview of these translational and pharmacological principles of HIPEC and aims to expose knowledge gaps that may direct further research to optimize the HIPEC procedure and ultimately improve survival for women with advanced ovarian cancer.

Gynecological malignancies and obesity

The global pandemic of obesity has had a significant impact on gynecological malignancies, most notably endometrial cancer. It has resulted in worldwide increases in the incidence of endometrial cancer and a change in patient demographics, resulting in more diagnoses than ever before being made in pre-menopausal women, who are often keen to pursue fertility-sparing treatments. Obesity increases the risk of gynecological cancers by creating a pro-carcinogenic environment of unopposed estrogen, hyperinsulinemia, and chronic inflammation. It can present both a diagnostic challenge and strongly influence management decisions, including the practicalities of performing surgery, increase anesthetic risks, and alter response rates to adjuvant and medical therapies. Obesity may also influence endometrial cancer mortality and certainly contributes to poorer overall survival due to an excess of deaths related to cardiovascular disease. Weight loss may well, therefore, be the key to the prevention of gynecological cancers and their recurrence.

Ovarian cancer screening: Current status and future directions

Ovarian cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through screening. Multimodal ovarian cancer screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel screening modalities and longitudinal biomarker algorithms offer potential improvements to future screening strategies as does the development of better risk stratification tools.

Population-based genetic testing for Women's cancer prevention

Germline mutations in cancer-susceptibility-genes (CSG) can dramatically increase womens' lifetime risk of ovarian, endometrial, breast and bowel cancers. Identification of unaffected carriers is important to enable proactive engagement with highly effective screening and preventive options to minimise cancer risk. Currently, a family-history model is used to identify individuals with CSGs. Complex regional referral guidelines specify the family-history criteria required before an individual is eligible for genetic-testing. This model is ineffective, resource intense, misses >50% CSG carriers, is associated with underutilisation of genetic-testing services and delays detection of mutation carriers. Although awareness and detection of CSG-carriers has improved, over 97% carriers remain unidentified. This reflects significant missed opportunities for precision-prevention. Population-based genetic-testing (PBGT) represents a novel healthcare strategy with the potential to dramatically improve detection of unaffected CSG-carriers along with enabling population risk-stratification for cancer precision-prevention. Several research studies have assessed the impact, feasibility, acceptability, long-term psychological outcomes and cost-effectiveness of population-based BRCA-testing in the Ashkenazi-Jewish population. Initial data on PBGT in the general-population is beginning to emerge and large implementation studies investigating PBGT in the general-population are needed. This review will summarise the current research into the clinical, psycho-social, health-economic, societal and ethical consequences of a PBGT model for women's cancer precision-prevention.

Systematic review of acceptability, cardiovascular, neurological, bone health and HRT outcomes following risk reducing surgery in BRCA carriers

Primary surgical prevention in the form of risk-reducing salpingo-oophorectomy (RRSO) is the most effective option and the gold standard for ovarian cancer (OC) risk-reduction, particularly given the absence of an effective national OC screening programme. However, premenopausal RRSO leads to premature surgical menopause with detrimental long-term health sequelae particularly in women who do not/are unable to take hormone replacement therapy (HRT). HRT uptake in women undergoing pre-menopausal oophorectomy appears low and is dependent on informed counselling, the safety of HRT and efficacy in mitigating the health sequelae of premature menopause. Acceptance of a central role for the fallopian tube in OC etiopathogenesis, coupled with the detrimental consequences of premature menopause, has led to the attractive proposal of early-salpingectomy with delayed oophorectomy as an alternative OC surgical prevention strategy in premenopausal women who have completed childbearing but decline or wish to delay RRSO. The successful implementation of risk reducing surgery for OC prevention depends on the acceptability of surgery to both, recipients (e.g. BRCA1/BRCA2 carriers) and intervention deliverers (healthcare professionals/researchers). Acceptability is also informed by an understanding of health outcomes following risk reducing surgery and the safety of HRT. It is therefore vital to understand the effects of surgery on important health outcomes such as cardiovascular health, neurological function and bone health. We present a comprehensive review of acceptability, the selected health outcomes mentioned above and HRT safety following risk reducing surgery.

Genetic testing for epithelial ovarian cancer

As the treatment of epithelial ovarian cancer (OC) moves further into personalised medicine, the importance of determining the presence or absence of inherited mutations in cancer susceptibility genes has grown. It is now becoming routine to test for germline mutations in the BRCA1 and BRCA2 genes, which are responsible for a significant proportion of hereditary epithelial OC and are established predictive biomarkers of potential benefit from poly ADP ribose polymerase (PARP) inhibitors. The identification of patients with hereditary OC allows the patient to benefit from personalised treatment, while allowing family members to undergo cascade testing, where identification of unaffected carriers can allow early detection, risk-reduction or prevention for both breast and OC, and ultimately improve long-term outcomes. Other susceptibility genes, include the Lynch Syndrome (mismatch repair) genes and several other genes involved in the homologous recombination pathway (HRD genes), are implicated in OC genesis, and are also becoming of increasing interest as therapeutic options grow for these patients. This review will highlight the importance of the early detection of a germline gene pathogenic variant, which informs on the clinical course of disease in a particular patient, and therefore, guides therapeutic management including risk reducing and personalised treatment.

Ovarian transposition and cervical cancer

Cervical cancer is the fourth most common female malignancy worldwide. As the focus of treatment is shifting towards balancing oncological outcomes with reproductive benefit, women are becoming increasingly aware of their fertility options. Cervical cancer is one of the primary malignancies where transposition of the ovaries may be indicated. Ovarian transposition should be performed in pre-menopausal women, undergoing pelvic irradiation to preserve ovarian function and prevent early menopause. The review discusses the available literature and synthesises a concise summary for gynaecologic oncology surgeons to counsel affected women. The paradoxical controversy, leading to its under use is acknowledged, due to the scarcity of published data with regard to functional outcomes, and the lack of clinical trials. In cervical cancer, ovarian transposition remains a safe fertility preservation (FP) option, which is associated with high ovarian function preservation, an acceptable rate of ovarian cysts and a negligible risk for metastases in the transposed ovaries.

Conservative (non-radical) surgery for stage IB1 cervical cancer

There has been lively debate in recent years following the publication of various retrospective case series and small cohort studies that suggest certain women presenting with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer (pre-2018 revised classification) may be treated by non-radical surgery, either simple hysterectomy or cone biopsy, where fertility preservation is required. A strictly defined histological criterion is necessary for selecting such cases, incorporating tumour dimensions including estimated tumour volume, lympho-vascular space invasion and pelvic lymph node status. Meta-analyses of these studies show that the oncological outcomes are comparable to the excellent results achieved by radical hysterectomy and radical trachelectomy. In addition, the fertility and pregnancy outcomes for cases treated by conisation are superior to cases managed by radical trachelectomy. Multi-centre, ethically approved, prospective studies are currently on-going, which will provide better quality evidence in an attempt to contribute to this debate, with the intention of improving outcomes, including quality of life, in women presenting with small-volume stage IB1 cervical cancer.

Fertility sparing treatment for cervical cancer

Imaging to assist fertility-sparing surgery

Cytological screening and human papilloma virus testing has led to diagnosis of cervical cancer in young women at an earlier stage. Defining the full extent of the disease within the cervix with imaging aids the decision on feasibility of fertility-sparing surgical options, such as extended cone biopsy or trachelectomy. High spatial resolution images with maximal contrast between tumour and surrounding background are achieved with T2-weighted and diffusion-weighted (DW) magnetic resonance imaging (MRI) obtained using an endovaginal receiver coil. Tumour size and volume demonstrated in this way correlates between observers and with histology and differences between MRI and histology estimates of normal endocervical canal length are not significant. For planning fertility-sparing surgery, this imaging technique facilitates the best oncological outcome while minimising subsequent obstetric risks. Parametrial invasion may be assessed on large field of view T2-weighted MRI. The fat content of the parametrium limits the utility of DW imaging in this context, because fat typically shows diffusion restriction. The use of contrast-enhanced MRI for assessing the parametrium does not provide additional benefits to the T2-weighted images and the need for an extrinsic contrast agent merely adds additional complexity and cost. For nodal assessment,

Maternal adnexal masses in pregnancy

Maternal adnexal masses are increasingly detected during pregnancy, primarily due to the widespread use of ultrasound in obstetrics. Most of them are functional cysts that resolve spontaneously. Lesions visualized by ultrasound in adnexal topography may be retroperitoneal or intraperitoneal (non-gynecologic or obstetric/gynecologic formations, such as pregnancy-related masses, subserosal uterine fibroids or true adnexal lesions). The largest number of adnexal lesions do not change their ultrasound morphology in pregnancy. However, endometriomas may decidualize, mimicking borderline or stage I invasive ovarian malignancies. The patient management can be conservative (ultrasound surveillance) or surgery. The decision depends on a series of factors including the risk of malignancy. Until mathematical models have been widely validated in pregnancy, the International Ovarian Tumor Analysis Group recommends using simple benign descriptors and expert subjective assessment to predict the risk of maternal adnexal malignancy in pregnancy. In the future, artificial intelligence could be useful.

Robotic radical hysterectomy after conization for patients with small volume early-stage cervical cancer

Laparoscopy and robotics are recommended for managing gynecological cancer, as they are associated with lower morbidity and comparable outcomes to open surgery. However, in the case of early cervical cancer, new evidence suggests worse oncological outcomes with these approaches compared to open surgery, though the limited number of robotic cases makes it challenging to draw definitive conclusions for this particular approach. The prior conization has been proposed as a strategy to reduce the risk of tumor spillage and contamination during minimally invasive (MIS) radical hysterectomy (RH). Retrospective studies have indicated that undergoing conization before RH is linked to a reduced risk of recurrences, especially in cervical tumors measuring less than 2 cm. Nevertheless, these studies lack the statistical power needed to definitively establish conization as a recommended step before RH. Furthermore, these studies do not have enough cases utilizing the robotic approach and specific conclusions cannot be drawn from this technique. The question of whether a subset of cases would benefit from preoperative conization and whether conization should be performed to recommend MIS over open surgery remains unanswered. Prospective clinical trials involving women diagnosed with early-stage cervical cancer <2 cm, randomized between undergoing conization before robotic RH or without prior conization are mandatory to assess the role of conization before robotic RH in cervical cancer.

Role of adjuvant and post-surgical treatment in gynaecological cancer

Adjuvant and post-operative therapy aimed at reducing the risk of disease recurrence and improving potential for cure can be broadly categorised into systemic and locoregional treatment. For epithelial ovarian cancer, cytoreductive surgery and platinum-based chemotherapy is the mainstay management. Maintenance therapy with PARPi is a state-of-the-art option for women with advanced disease following complete or partial response to first-line platinum-based chemotherapy, particularly those with BRCA mutations. Adjuvant treatment for endometrial cancer depends mostly on FIGO staging and histopathological risk factors. For cervical cancer, adjuvant chemoradiation is indicated after surgery in women with close or positive resection margins and positive nodes. Generally, recommendations for adjuvant therapy should be individualised and reviewed at the multidisciplinary tumour board meeting, and the decision for adjuvant therapy should be balanced with treatment toxicity. The overview of the role of adjuvant and post-surgical treatment in gynaecological cancers will be discussed in this chapter.

Radical vaginal trachelectomy

Radical vaginal trachelectomy (RVT) is the oldest fertility-sparing procedure for stage 1b cervical cancer. For that reason, there are more published data for RVT than for all the other radical trachelectomy approaches. However, there are no randomised controlled studies between RVT and radical hysterectomy proving the comparability of survival and no randomised controlled studies comparing a vaginal approach with open, standard laparoscopy and robotic approaches. This article intends to describe the case selection, the procedure and outcomes for RVT.

Overview of fertility sparing treatments for cervical cancer

Until the late 1980s, the mainstay of treatment for cervical cancer has been either hysterectomy or radiotherapy. From the mid to late 1990s, surgical treatments have been focussed more on sparing fertility by preserving the corpus of the womb with trachelectomy or even conserving part of the cervical stroma with a cone biopsy. In carefully selected cases, less radical treatment that preserves the uterus has been considered safe. However, these approaches can be associated with specific operative and obstetric complications such as stitch ulceration, cervical stenosis, late miscarriage, and premature labour. Most guidelines agree that the management of such patients should be centralised in a unit with specialist gynaecological oncology, radiology, and histopathology services supported by specialist cancer nurses.

Fertility sparing treatment in cervical cancer management in pregnancy

The article focuses on fertility-sparing management during pregnancy and obstetrical management after fertility-sparing surgery. Over the years, more women in developed countries tend to delay childbirth to a later age, which leads to cervical cancer more often diagnosed during pregnancy. The advances in our understanding of prognosis and treatment options in these patients have helped us to address avenues and to circumvent standard therapy and fetal demise, respecting maternal and fetal chances. Childbearing trends also lead to an increase in the number of patients considering fertility-sparing management when diagnosed with cervical cancer. Such management represents a challenge for obstetricians as prior cervical surgery is a known risk factor for various adverse events. These include decreased fertility, second trimester miscarriage, preterm labor, or preterm premature rupture of membranes. Watchful follow-up and various prophylactic measures are keys when striving for the best possible outcome.

Adjuvant treatment in cervical, vaginal and vulvar cancer

Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.

The effects of cancer treatments on uterine function

Current and emerging data sources for assessment of ovarian toxicity in children, adolescents and young adults with cancer

Adjuvant and post-surgical treatment in endometrial cancer

Endometrial cancer (EC) usually presented as a localized disease at diagnosis (67%), 20% of patients diagnosed with regional spread, and distant metastasis accounted for 9%. The standard treatments include hysterectomy, bilateral salpingo-oophorectomy, and pelvic with/without paraaortic lymph node dissection/biopsy. Adjuvant therapy is arranged according to risk factors and stages. Risk group classification varied among different guidelines and studies and evolved with time. Adjuvant modalities include chemotherapy, radiotherapy, chemoradiotherapy, antiangiogenesis agents, immune checkpoint inhibitors, and multi-target agents. We review the recent literature to incorporate important advances in trial results, real-world big data, and knowledge in biomarkers of EC to update appropriate adjuvant therapy and post-surgical treatment of EC patients.

Robotic surgery in ovarian cancer

Ovarian cancer (OC) represents one of the most lethal cancers in women. The aim of surgical treatment is complete cytoreduction in advanced stages and a surgical staging in early stages. Although the guidelines still suggest laparotomy as the standard approach, in recent years minimally invasive surgery (MIS) has become increasingly popular in the treatment of OC, especially in early stages, because the 5-year relative survival exceeds 90% and the patients' quality of life cannot be overshadowed. However, MIS has been demonstrated to have a role even in advanced stages, in the prediction of optimal cytoreduction, identification patients who may benefit from neoadjuvant chemotherapy, and, more recently, in the interval debulking surgery, as in selected cases of secondary cytoreduction for recurrent ovarian cancer. The aim of this review is to describe the MIS (especially robotic surgery), with its advantages and pitfalls, in the treatment of OC.

Borderline ovarian tumours: A comprehensive review of published evidence

Borderline Ovarian Tumours (BOTs) comprise 15-20 % of all epithelial ovarian tumours. BOTs are characterised by increased mitotic activity but lack infiltrative destructive growth and stromal invasion. Several dilemmas and controversies have been discussed in the literature regarding BOT management including surgical approach (radical versus fertility-sparing surgery), surgical route (open versus laparoscopic surgery) and impact on disease recurrence, follow-up protocols/modalities (imaging, serum biomarkers), role of completion surgery, lymph node dissection during staging, adjuvant chemotherapy, as well as use of Hormone-Replacement Therapy (HRT) post-surgery. We performed a structured narrative review on Medline and Cochrane Library Databases to identify studies pertaining to the management of BOTs. Identifying areas of agreement and outstanding uncertainty are integral to optimise robust treatment regimens for BOT management and improve the Quality of Life (QoL) and clinical outcomes for patients. We discuss a framework of recommendations to counsel, manage and follow-up women diagnosed with BOT.

Is there a need for screening of cervical HPV infections and carcinoma?

Antenatal cervical screening aims to detect cervical intraepithelial neoplasms as precancerous lesions and invasive cervical cancer. Whether this screening is performed routinely during pregnancy varies depending on each country's screening participation rates, guidelines, and the risks to the pregnant woman. In some countries with the high rate of routinely implemented cervical screening among the target women, women are recommended to defer cervical screening intentionally to post-delivery, though having screening in consultation with physicians may be possible if routine screening overlaps. However, when cervical screening rate in fertile women is low and the incidence of cervical cancer is high, cervical screening during pregnancy may play an important role in the early detection of cervical cancer. Cervical screening using high-risk human papillomavirus (HPV) testing is accepted worldwide as a highly sensitive and objective test method, and it should replace traditional primary cervical cytology in the future. However, the benefits and disadvantages of using HPV testing in pregnant women is unclear because a false positive rate may be increased due to pregnant women being generally under an immunosuppressed condition.

Sentinel Lymph node detection in endometrial cancer - Anatomical and scientific facts

Anatomical and functional aspects of the lymphatic drainage of the uterine corpus in endometrial cancer are demonstrated. Main lymphatic pathway runs along the upper pelvic pathway from the uterine artery first line to the medial external iliac nodes, followed by the lateral external and common iliac node basin. The second important pathway runs along the ovarian vessels directly to the paraaortic nodes. Pathways may visualized best by injection of indocyanine green (ICG) into the uterus. In contrast to the upper pelvic pathway visualized by cervical injection, the paraaortic drainage can only be marked by corporal injection. Lymphatic drainage works downstream (peripheral to central, with respect to vascular valves) only. Clinically, pelvic sentinel node excision replaced systematic lymphadenectomy for diagnostic purposes and even paraaortic node staging can be omitted in most of pelvic node negative patients. For therapeutic purposes compartmental resection of the uterus together with its lymphovascular system and first line nodes "en bloc" could be an option as performed in peritoneal mesometrial resection/targeted compartmental lymphadenctomy (PMMR/TCL).

Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.

Adjuvant and post-surgical treatment in non-epithelial ovarian cancer

Non-epithelial cancers arising from the ovary are uncommon malignancies. Germ cell tumors of the ovary arise from primordial germ cells, and sex cord-stromal tumors of the ovary represent a cluster of tumors arising from the sex cord and stromal compartment. Most patients diagnosed with germ cell tumors are young adults and adolescent females. In contrast, ovarian sex cord-stromal tumors more commonly occur in a mature age group. Advances in the adjuvant management of non-epithelial ovarian cancer following optimal surgical and pathological staging have improved patient survival outcomes. In addition, active surveillance is preferentially assigned to patients diagnosed with stage I germ cell tumor, stage 1A grade 1 immature teratoma, stage 1A yolk sac tumor, and stage 1AI sex cord-stromal tumors. This article discusses the importance of selecting the adjuvant treatment approach most suitable to the patients' surgical and pathological stages, thereby safeguarding patient outcomes.

Primary HPV screening for cervical cancer

Cytology-based cervical screening had unequivocal success in reducing the incidence and mortality of cervical cancer in the last century. The recognition of the role of human papillomavirus (HPV) as a necessary cause of cervical cancer led to the development of HPV testing. Gradually, there has been a shift from reflex HPV testing for mild cytological abnormalities, to co-testing with cytology and HPV, and lately to primary HPV screening, based on evidence from well-designed large randomized controlled trials and meta-analyses. Advantages of primary HPV screening include higher sensitivity to detect pre-neoplastic lesions, better re-assurance with a negative test, and safe prolongation of screening intervals. However, clinicians and policy makers must ensure the availability of clinically validated HPV assays and triage protocols of screen positive cases prior to implementation of primary HPV screening. This is likely to reduce potential harm from over-treatment as well as extra burden on the health care system.

HPV vaccination and cancer prevention

Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.

Minimally invasive radical trachelectomy: Considerations on surgical approach

Current evidence supports that radical trachelectomy is a safe and feasible alternative to patients with early-stage cervical cancer who wish to preserve fertility. In addition, published retrospective literature supports that oncologic outcomes are equivalent to those of radical hysterectomy. First published as a vaginal approach, a number of other approaches have been reported including laparotomic, laparoscopic, and robotic. In 2018, the first ever prospective randomized trial (LACC) comparing open vs. minimally invasive radical hysterectomy showed worse disease-free and overall survival for the minimally invasive (both laparoscopic and robotic) approach than the open approach. This landmark publication raised concerns regarding the oncologic safety of minimally invasive radical trachelectomy. In the United States, minimally invasive became the dominant approach by 2011 for radical trachelectomy. Given that radical trachelectomy is an infrequent performed procedure, only small retrospective studies, systematic reviews, and large database studies have been published. These studies are limited by their retrospective nature, small sample size, patient selection bias, unbalanced groups, and sequential surgical approach comparisons. However, the available evidence thus far shows that oncologic outcomes for both open and minimally invasive radical trachelectomy are equivalent. Given the rarity of the procedure and the low recurrence and death rates of patients with early-stage cervical cancer undergoing radical trachelectomy, a prospective randomized trial seems unlikely. A multi-institutional international registry study (International Radical Trachelectomy Assessment - IRTA - study) has been recently completed evaluating open vs. minimally invasive radical trachelectomy. There are three ongoing prospective studies evaluating the possibility of less radical surgery in a low-risk early-stage cervical cancer population, ConCerv, SHAPE, and GOG 278. We look forward to the final results of these studies that will hopefully shed light on the optimal treatment option for patients with early-stage cervical cancer wishing to preserve fertility. This article will review the most impacting publications comparing open vs. minimally invasive radical trachelectomy and analyze the limitations of the current available literature.

The role of molecular tests for adjuvant and post-surgical treatment in gynaecological cancers

The adjuvant and post-surgical treatment of gynaecological cancers has historically been guided by the estimation of relapse risk based on clinicopathological factors determined at the time of cancer diagnosis. The recent advancement of genomic and molecular characterisation of gynaecological cancers has begun to shift paradigms in the selection of adjuvant treatment strategy. Recent data regarding the predictive and/or prognostic value of molecular tests in the treatment of advanced ovarian cancer as well as early stage endometrial cancer have been the first such examples to enter adjuvant treatment guidelines for these diseases. In this article, we discuss the current state and future development of molecular assays for gynaecological cancers and how they impact upon treatment selection for ovarian, endometrial and cervical cancers in the post-surgical setting.