Hematology/Oncology Clinics of North America

Surgery for Recurrent Ovarian Cancer

The use of secondary cytoreductive surgery before standard chemotherapy in recurrent ovarian cancer is controversial. Several groups have identified patient and disease factors that correlate with benefit from surgery. Complete gross resection of disease is the most important factor, and selection criteria have been developed and validated to predict this outcome. Recently, 3 parallel multicenter randomized controlled trials of secondary cytoreduction were reported and have shown mixed results but a meta-analysis suggests a benefit, particularly, in those with complete gross resection of disease.

Cervical Cancer

Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions.

Placental Site Trophoblastic Tumors and Epithelioid Trophoblastic Tumors

Placental site trophoblastic disease (PSTT) and epithelioid trophoblastic tumor (ETT) are the rarest forms of gestational trophoblastic neoplasia (GTN) with unique clinical features and treatment considerations. Unlike other GTN, human chorionic gonadotropin (hCG) is minimally, if at all, elevated. Additionally, unlike other GTN, WHO risk scores are not applied to PSTT/ETT. Management of PSTT/ETT is predominately surgical with hysterectomy and possible lymphadenectomy. There are case reports of fertility sparing surgery for uterine confined disease. Multi-agent chemotherapy ± pembrolizumab is added for those with high risk features defined as advanced stage disease and those diagnosed ≥48 months from the antecedent pregnancy. Survival for early stage, low risk disease remains quite good but the prognosis for high-risk disease is poor and an scenario for which novel treatments are needed.

Genetics and Genomics of Gestational Trophoblastic Disease

This article focuses on hydatidiform mole (HM), which is the most common form of gestational trophoblastic disease and the most studied at the genomic and genetic levels. We summarize current laboratory methods to diagnose HM, discuss their limitations and advantages, and share the lessons we have learned. We also provide an overview of the history of recurrent HM, their known genetic etiologies, and the mechanisms of their formation.

Diagnosis and Management of Molar Pregnancies

Complete and partial molar pregnancies arise from abnormal fertilization with marked proliferation of syncytiotrophoblasts. Earlier diagnosis has reduced the frequency of severe medical complications at presentation; however, the risk of progression to gestational trophoblastic neoplasia (GTN) has remained unchanged. Initial assessment should include serum hCG measurement after physical examination, laboratory testing for organ dysfunction, and Doppler ultrasound. Following uterine evacuation, pathologic assessment can distinguish complete from partial moles or non-molar gestations. Close surveillance is essential for the timely diagnosis of GTN. Cure rates and subsequent obstetrics outcomes are excellent, but all patients should be referred for psychologic support and expert level care.

Diagnostic Accuracy of Biomarkers and International Ovarian Tumor Analysis Simple Rules in Diagnosis of Ovarian Cancer

This study investigated whether combining International Ovarian Tumor Analysis (IOTA) Simple Rules with tumor biomarkers would improve the diagnostic accuracy for early detection of adnexal malignancies. Receiver operating characteristic curve analysis of suspected adnexal tumors was performed in 226 women admitted for surgery at the University Clinical Center of Kosovo. Primary outcome was the diagnostic accuracy of the combination of adnexal mass biomarkers and IOTA Simple Rules. IOTA Simple Rules combined with biomarker indications increased the diagnostic accuracy of classifying adnexal masses. Data analysis of individual measures showed that ferritin had the lowest rate of sensitivity.

An Overview of Cervical Cancer Prevention and Control in Latin America and the Caribbean Countries

Cervical cancer is a health crisis affecting women and their families across the world. It is known that developed countries have comprehensive protocols with recommendations regarding workforce, expertise, and medical resources to address this common cancer among women. In contrast, disparities in addressing cervical cancer remain present in Latin America and Caribbean countries. Here, we reviewed the current strategies of cervical cancer prevention and control in the region.

The Landscape of Personalized Medicine in Gynecologic Cancer

Gynecologic malignancies are a heterogenous group of tumors driven by a wide variety of molecular alterations. Molecular profiling has become increasingly useful in the development of novel biomarkers, screening tools, and targeted therapeutic agents. The purpose of this article is to provide an overview of the current usage of personalized medicine in the field of gynecologic oncology.

Sexual Health Following Diagnosis and Treatment of Gynecologic Cancer

Gynecologic cancer treatments often lead to increased sexual concerns, which often are not addressed. Screening should be performed in a standardized fashion both routinely and frequently. Various treatment options are available and should be offered to improve quality of life. Referrals to specialty clinics can be made when available.

Health Care Disparities in Gynecologic Oncology

Antibody–Drug Conjugates for the Treatment of Gynecologic Cancer

Emerging Therapeutic Targets for Platinum-Resistant Ovarian Cancer

Recurrent platinum-resistant ovarian cancer represents a significant therapeutic challenge, characterized by poor responses to standard chemotherapy and limited survival outcomes. This chapter comprehensively reviews the biological mechanisms underlying platinum resistance, including alterations in DNA repair pathways, intracellular drug transport, evasion of apoptosis, tumor microenvironment adaptations, and cancer stem cell dynamics. Emerging therapies targeting these mechanisms are discussed in detail, along with promising strategies that combine these therapies. Clinical trial data are discussed to highlight advances in overcoming platinum resistance and the potential for biomarker-driven treatment approaches. The chapter emphasizes the importance of targeting tumor heterogeneity and resistance mechanisms through novel therapies and personalized strategies to improve outcomes in patients with recurrent platinum-resistant ovarian cancer.

Mitogen-Activated Protein Kinase Driven Rare Gynecologic Cancers and Evolving Therapeutic Targets

The mitogen-activated protein kinase (MAPK) cascade is a critical pathway involved in cancer cell survival as well as resistance to drug therapy. Phosphorylation of extracellular signal-regulated kinase 1 (ERK1) and extracellular signal-regulated kinase 2 (ERK2), the final effectors of the MAPK pathway, results in activation of multiple substrates that are responsible for cellular proliferation, differentiation, survival, and migration. This review will focus on our current understanding of 2 types of rare gynecologic cancers that frequently harbor MAPK alterations, low-grade serous ovarian cancer and mesonephric/mesonephric-like gynecologic neoplasms, and how this understanding may change our future treatment of these diseases.

Surgical Management of Gynecologic Cancers

This article addresses the role of surgery in the management of gynecologic cancers with liver metastases. The authors review the short-term and long-term outcomes of aggressive resection through retrospective and randomized studies. Although the data supporting aggressive resection of liver metastasis are largely retrospective and case based, the randomized control data to address neoadjuvant versus chemotherapy have been widely criticized. Residual disease remains an important predictor for survival in ovarian cancer. If a patient cannot achieve near optimal cytoreduction, radical cytoreductive procedures, such as hepatic resection, should be considered for palliation only.

Ultra High-risk Gestational Trophoblastic Neoplasia

Ultra high-risk gestational trophoblastic neoplasia (GTN) refers to patients with World Health Organization prognostic risk scores of at least 13. The mortality risk for these patients averages 30%. Ultra high-risk GTN more frequently presents with higher tumor volume, liver and/or brain metastases, and very high human chorionic gonadotropin levels. The diagnostic evaluation must include a thorough evaluation for central nervous system disease. Prompt initiation of cisplatin - etoposide induction chemotherapy reduces the risks of early death. Collaborative services such as neurosurgery, radiation oncology, and interventional radiology may be required to manage hemorrhagic lesions.

Initial Diagnosis and Treatment of Low-Risk Gestational Trophoblastic Neoplasia

Gestational trophoblastic neoplasia (GTN) is a rare form of cancer that is treated according to the World Health Organization (WHO) risk score, which predicts responsiveness to single-agent chemotherapy. Patients with WHO risk scores ≤6 have low-risk GTN, for which cure rates near 100%. Most women with low-risk GTN will respond to single-agent chemotherapy, which is given with either methotrexate or dactinomycin, and allows women to retain their fertility. This article also discusses less common treatment paradigms including second dilation and curettage and hysterectomy, as well as the emerging role of immunotherapy in managing low-risk GTN.

Advances in Cervical Cancer

Cervical cancer continues to represent an immense burden worldwide. Fortunately, in all stages of the disease and therapeutic modalities there have been significant advances in the past 5 years with the promise of improving oncologic outcomes and decreasing morbidity. The introduction of immunotherapy into the care of patients with metastatic and recurrent cervical cancer, a disease with a historically poor prognosis and limited treatment options, has altered the standard of care.

Pathology of Gestational Trophoblastic Disease (GTD)

Gestational trophoblastic disease (GTD), comprising hydatidiform moles (HM) and gestational trophoblastic tumors (GTT), is extremely rare. HM originate from villous trophoblast and are considered preneoplastic. GTT originate from the intermediate, largely extravillous trophoblast and includes choriocarcinoma, placental site trophoblastic tumor, epitheloid trophoblastic tumor, and mixed trophoblastic tumor. The abnormal (non-molar) villous lesions, non-malignant tumour-like conditions, and non-gestational tumors add to the diagnostic dilemma. The correct diagnosis and classification of these rare conditions are important. This review intends to provide an update on changes in the World Health Organization classification and focusses on the morphologic aspects in diagnosis of GTD.

Sentinel Lymph Node Sampling in Endometrial Cancers

The surgical staging of endometrial cancer has changed in recent years to include sentinel lymph node (SLN) biopsy as a tool to replace regional lymphadenectomy. This has afforded surgeons the ability to preserve surgical staging information, valuable for adjuvant therapy prescription, while minimizing associated morbidities, such as lymphedema. Although SLN biopsy has been established as being highly accurate in detecting metastatic disease, including in patients with high-grade cancers, future studies should focus on establishing the value of this technique with respect to patient survival and its role in concert with molecular markers to individualize and optimize treatment outcomes.