Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate.

Cancer outcomes are largely measured in terms of disease-free survival or overall survival, which is highly dependent on timely diagnosis and access to treatment methods available within the country's existing health care system. Although cancer survival rates have markedly led in the past few decades, any improvement in the 5-year survival of gynecologic cancers has been modest, as in the case of ovarian and cervical cancers, or has declined, as in the case of endometrial cancer. The lack of effective screening options contributes to many women presenting with advanced-stage disease and the need for radical approaches to treatment. Although treatment for early-stage disease can lead to a cure, advanced-stage disease is fraught with a high potential for morbidity and mortality, and recent clinical trials have aimed to assess the noninferiority of minimally invasive options versus aggressive surgical approaches. Of particular interest is fertility-sparing treatments for endometrial and cervical cancers, which have recently been on the rise among younger women. Balancing morbidity with the risk of mortality, and loss of fertility and quality of life requires a targeted patient-centered approach to treatment. This is an ongoing area of intense research and sometimes may challenge current treatment paradigms. In this two-part review, we present an overview of current approaches to gynecologic cancer treatment and the need to de-escalate radical surgical approaches and preserve fertility. We also review the intricacies of ovarian and advanced endometrial cancer treatment, exploring the nuances in surgical debulking timing and its impact on outcomes.

Antibody-Drug Conjugates in Gynecologic Cancers.

OPINION STATEMENT: Antibody-drug conjugates (ADCs) are a novel class of targeted cancer therapies with the ability to selectively deliver a cytotoxic drug to a tumor cell using a monoclonal antibody linked to a cytotoxic payload. The technology of ADCs allows for tumor-specificity, improved efficacy, and decreased toxicity compared to standard chemotherapy. Common toxicities associated with ADC use include ocular, pulmonary, hematologic, and neurologic toxicities. Several ADCs have been approved by the United States Food and Drug Administration (FDA) for the management of patients with recurrent or metastatic gynecologic cancers, a population with poor outcomes and limited effective treatment options. The first FDA-approved ADC for recurrent or metastatic cervical cancer was tisotumab vedotin, a tissue factor-targeting agent, after demonstrating response in the innovaTV 204 trial. Mirvetuximab soravtansine targets folate receptor alpha and is approved for use in patients with folate receptor alpha-positive, platinum-resistant, epithelial ovarian cancer based on results from the SORAYA trial. While there are no FDA-approved ADCs for the treatment of uterine cancer, trastuzumab deruxtecan, an anti-human epidermal growth factor receptor 2 (HER2) agent, is actively being investigated. In this review, we will describe the structure and mechanism of action of ADCs, discuss their toxicity profiles, review ADCs both approved and under investigation for the management of gynecologic cancers, and discuss mechanisms of ADC resistance.

Healthcare access dimensions and uterine cancer survival: a national cancer database study.

Objective: Disparities exist throughout diagnosis, treatment, and survival for Black patients with uterine cancer. There is limited data on how several healthcare access (HCA) dimensions contribute to these disparities in patients with advanced stage uterine cancer. Methods: Using the National Cancer Database (NCDB), we identified patients aged 40-89 years with Stage III-IV uterine cancer between 2004-2015 who received chemotherapy and/or radiotherapy. Race/ethnicity were classified as non-Hispanic (NH)-Black, Hispanic, and NH-White. Variables defined in the NCDB were used to assess HCA affordability, availability, and accessibility. Kaplan-Meier estimates, log-rank test, and multivariable Cox proportional hazards models were used to analyze overall survival. Results: Of 43,134 patients, 78.8% of the cohort identified as NH-White, 15.3% NH-Black, and 5.9% Hispanic. NH-Black patients were the most likely to have type II (75.6% vs. 53.9% and 55.4%) and stage IV (40.8% vs. 30.7% and 32.3%) disease compared to NH-White and Hispanic patients. NH-Black patients were more likely than NH-White and Hispanic patients to have government funded insurance (58.6% vs. 50.3% and 50.4%), live in low-income areas (46.4% vs. 14.2% and 29.9%), and receive only chemotherapy (53.5% vs. 43.1% and 46.2%). Having private insurance and receiving treatment at an academic facility were positive predictors of survival. NH-Black patients had worse survival than NH-White patients after adjusting for clinical characteristics and healthcare access dimensions (HR 1.29; 95% CI 1.24, 1.34). Conclusion: While HCA affordability and availability predicted survival in patients with advanced stage uterine cancer, additional factors contribute to racial disparities. Compared to NH-White patients, NH-Black patients had more aggressive disease, received only chemotherapy rather than combined therapy, and had worse survival regardless of cancer subtype. Additional dimensions of healthcare access must be explored to remedy uterine cancer disparities.

Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial.

OBJECTIVE: To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy. METHODS: This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power. RESULTS: Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable. CONCLUSIONS: Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04563130.

Peripartum Pubic Symphysis Diastasis.

Importance: Peripartum separation of the pubic symphysis is a rare but potentially severe complication of childbirth, which may lead to prolonged immobilization. Thus, prompt diagnosis and treatment are paramount. Objective: The purpose of this review is to define peripartum separation of the pubic symphysis and provide a thorough review of its etiology, clinical manifestations, diagnostic imaging techniques, management, and prognosis. Evidence Acquisition: This was a literature review using PubMed and Google Scholar. Results: Peripartum pubic symphysis separation is defined as disruption of the pubic symphysis joint and ligamentous structures with greater than 1 cm of separation during delivery. Risk factors include fetal macrosomia, nulliparity, and precipitous labor. Patients often present with a sensation of something "giving way" in the pubic symphysis area at the time of delivery, or with severe pain in the pubic symphysis region with attempted mobilization postpartum. In severe cases, associated hematomas, pelvic fractures, sacroiliac joint disruption, and urinary tract injury may be seen. Imaging such as x-ray or ultrasound may be used to confirm the diagnosis. Although most patients recover well with conservative management, orthopedic surgical intervention may be indicated in more severe or unresolved cases. Conclusions and Relevance: Pubic symphysis separation is increasingly identified peripartum due enhanced accessibility and utilization of imaging modalities. It can be debilitating and lead to prolonged immobility postpartum. Therefore, early recognition and diagnosis are important, as this can guide decision-making for management. A multidisciplinary team approach, including coordination with obstetrics, orthopedic surgery, physical therapy, and occupational therapy should be used for early detection and treatment to ensure optimal patient outcomes.