A review of the state of cervical cancer: updates from prevention to recurrent disease.

PURPOSE OF REVIEW: To summarize the recent updates in cervical cancer from prevention and early detection to the management of early stage and recurrent disease as well as future areas of exploration. RECENT FINDINGS: The importance of the human papilloma virus vaccine and screening continue to make an impact in reducing the global burden of cervical cancer. In early-stage, low risk disease, new studies have demonstrated the role of less radical surgery with similar disease related outcomes. Efforts to improve outcomes in locally advanced cervical cancer have been reported. The incorporation of adjuvant chemotherapy, novel agents and checkpoint inhibitors, with the latter impacting disease free survival. In advanced/recurrent disease, the role of immunotherapy continues to make an impact and, in addition to recurrent disease, has now moved to the frontline for patients with programmed cell death ligand 1 expression. Tisotumab vedotin, an antibody drug conjugate, and other novel agents continue to be studied in this setting. SUMMARY: In this review, we discuss prevention measures and the outcomes of recent trials in all stages of cervical cancer. As therapies continue to evolve, ongoing trials and new areas of exploration will continue to identify opportunities to improve survival in cervical cancer.

A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.

Optimal overall treatment time for adjuvant therapy for women with completely resected, node-positive vulvar cancer.

INTRODUCTION: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva. MATERIALS AND METHODS: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations. RESULTS: A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001-1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024-1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024-1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693-0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001-1.007], p = 0.007). CONCLUSION: Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva.

Fertility-sparing surgery and survival among reproductive-age women with epithelial ovarian cancer in 2 cancer registries.

BACKGROUND: This study examined predictors of fertility-sparing surgery (FSS) among reproductive-age women diagnosed with epithelial ovarian cancer (EOC). In addition, relationships between FSS and survival were assessed in models stratified by tumor characteristics. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database (NCDB) were queried for women 44 years old or younger with a primary EOC. FSS included unilateral salpingo-oophorectomy and uterine preservation, whereas surgeries including bilateral salpingo-oophorectomy and hysterectomy were categorized as non-FSS. Logistic regression was used to estimate multivariable-adjusted odds ratios and 95% confidence intervals (CIs) for associations between clinical characteristics (eg, age at diagnosis and race) and FSS odds. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for FSS and overall survival in subgroups defined by stage and grade or by stage and histology. Analyses were stratified by database (SEER vs NCDB). RESULTS: This analysis included 9017 women (SEER, n = 3932; NCDB, n = 5085) with EOC diagnosed between the ages of 15 and 44 years. In both cohorts, factors associated with significantly higher FSS odds included a younger age, a more recent ovarian cancer diagnosis, and no adjuvant chemotherapy. FSS was significantly associated with lower overall survival among women with stage II to IV, serous EOC (SEER HR, 1.61; 95% CI, 1.22-2.12). Significant associations between FSS and survival were not observed in other subgroups defined by stage and grade or by stage and histology. CONCLUSIONS: FSS appears to be safe for certain women with EOC but was related to poor survival among women with advanced-stage, serous EOC. Confirmatory studies with information on fertility intentions are needed.

Race-driven survival differential in women diagnosed with endometrial cancers in the USA.

OBJECTIVE: African American women are increasingly being diagnosed with advanced and type II histology endometrial cancers. Outcomes have been observed to be worse in African American women, but whether or not race itself is a factor is unclear. We sought to evaluate the rates of diagnosis and outcomes on a stage-by-stage basis with respect to race using a large national cancer registry database. METHODS: The National Cancer Data Base was searched for patients with surgically staged non-metastatic endometrial cancer between 2004 and 2015. Women were excluded if surgical stage/histology was unknown, there was no follow-up, or no information on subsequent treatment. Pairwise comparison was used to determine temporal trends and Cox hazards tests with Bonferroni correction were used to determine overall survival. RESULTS: A total of 286 920 women were diagnosed with endometrial cancer and met the criteria for analysis. Median follow-up was 51 months (IQR 25.7-85.3). In multivariable models, in women with stage I disease, African American women had a higher risk of death than Caucasian women (HR 1.262, 95% CI 1.191 to 1.338, p<0.001) and Asian/Pacific Islander women had a lower risk of death than Caucasian women (HR 0.742, 95% CI 0.689 to 0.801, p<0.001). This held for African American women with stage II type I and type II disease (HR 1.26, 95% CI 1.109 to 1.444, p<0.001 and HR 1.235, 95% CI 1.098 to 1.388, p<0.001) but not for Asian/Pacific Islander women. African American women with stage IIIA-B disease also had a higher risk of death for type I and type II disease versus Caucasian women (HR 1.221, 95% CI 1.045 to 1.422, p=0.010 and HR 1.295, 95% CI 1.155 to 1.452, p<0.001). Asian/Pacific Islander women had a lower risk of death than Caucasian women with type I disease (HR 0.783, 95% CI 0.638 to 0.960, p=0.019) and type II disease (HR 0.790, 95% CI 0.624 to 0.999, p=0.05). African American women with stage IIIC1-2 had a higher risk of death with type I disease (HR 1.343, 95% CI 1.207 to 1.494, p<0.001) and type II disease (HR 1.141, 95% CI 1.055 to 1.233, p=0.001) whereas there was no significant difference between Caucasian women and Asian/Pacific Islander women. CONCLUSION: Race appears to play an independent role in survival from endometrial cancer in the USA, with African American women having worse survival on a stage-for-stage basis compared with Caucasian women.

Radiation-associated Angiosarcoma Mimicking Fallopian Tube High-grade Serous Carcinoma in a Woman With De Novo Li-Fraumeni Syndrome.

We present a case study of a woman with history of rectal adenocarcinoma, and a new diagnosis of radiation-associated angiosarcoma mimicking fallopian tube high-grade serous carcinoma who was subsequently found to have de novo Li-Fraumeni syndrome. Our objective is to highlight angiosarcoma as a potential pitfall in the diagnosis of high-grade serous carcinoma.

Recurrent low grade serous ovarian cancer in a 20 year old woman: A case from the Ohio State University College of Medicine.

A 20 year old with recurrent low-grade serous carcinoma (LGSC) is discussed. The differential diagnosis, pathology, epidemiology, treatment options are discussed. Focus on the molecular pathways of LGSC and the implications of the diagnosis on fertility are highlighted.

Evaluation of the Hematologic Safety of Same Day Versus Standard Administration (24- to 72-Hour Delay) of Pegfilgrastim in Gynecology Oncology Patients Undergoing Cytotoxic Chemotherapy.

OBJECTIVE: We assessed the safety and efficacy of administration of pegfilgrastim on the same day compared with standard administration 24 to 72 hours after chemotherapy in patients with gynecologic malignancies. METHODS: A retrospective review was conducted on patients undergoing pegfilgrastim to mitigate the myelosuppressive consequences of chemotherapy. The primary outcome was incidence of grade 3 to 4 neutropenia following pegfilgrastim for same-day administration (D1) versus standard administration (D2+). Secondary outcomes included dose delay, regimen change, hospitalization due to neutropenia, and incidence of febrile neutropenia. RESULTS: Four hundred twenty-one patients with 2071 administrations of pegfilgrastim were included. Five hundred six administrations of pegfilgrastim were given on D1 compared with 1565 administrations on D2+. The most common malignancy was ovarian cancer (79.1%), followed by endometrial (14.5%). Comparing the D1 and D2+ cohorts, noninferiority was not established for the incidence of grade 3 to 4 neutropenia (2.6% vs 1.8%, adjusted relative risk [aRR], 1.6; 90% confidence interval [CI], 0.87-3.2) or dose modification (6.5% vs 4.9%; aRR, 1.3; 90% CI, 0.9-1.8). However, the rate of treatment delays (7.3% vs 9.4%; aRR, 0.8; 90% CI, 0.6-1.1) in the D1 and D2+ groups suggested that delays in the D1 group were not more common than in the D2+ group. CONCLUSIONS: The incidence of hematologic toxicities and dose modification in patients receiving same-day pegfilgrastim were not as low as in those undergoing standard administration. However, treatment delays were found to be no more frequent in those receiving same-day pegfilgrastim versus standard administration. Same-day administration of pegfilgrastim is a reasonable option.

Cancer and pregnancy: an overview for obstetricians and gynecologists.

A relatively rare occurrence, pregnancy-associated cancer affects approximately 1 in 1000 pregnancies. Optimizing treatment of the cancer and minimizing harm to the fetus are often dependent on the extent of disease, treatment options required, and the impact on the pregnancy as well as the gestational age of pregnancy. When malignancy is diagnosed, the obstetrician-gynecologist plays a key role in the diagnosis, initial evaluation, and coordination of patient care. Furthermore, the obstetrician-gynecologist may be asked to assist in fertility planning for young women with a new diagnosis of cancer and may be responsible for addressing questions about family-planning needs and the safety of future pregnancy. Therefore, the purpose of this article was to provide the obstetrician-gynecologist with a relevant overview of the current literature regarding concurrent pregnancy and cancer diagnoses, management options, including maternal and neonatal outcomes, as well as the future needs of young women diagnosed with cancer who desire fertility preservation.

Reproductive counseling, contraception, and unplanned pregnancy in fertile women treated by gynecologic oncologists.

We sought to identify how gynecologic oncologists approach reproductive counseling for their fertile, reproductive age patients, and their experience with unplanned pregnancies. Members of the Society of Gynecologic Oncology (SGO) were surveyed electronically regarding consistency of counseling patterns of contraception and fertility concerns, most and least common contraceptive methods utilized, referral patterns, and incidence of unplanned pregnancy. Of the 1424 SGO members identified, 261 participated in the questionnaire, yielding a response rate of 18%. Eighty-two percent of respondents agreed unplanned pregnancy is a potential problem, but only 57% believed their patients understood unplanned pregnancy is possible during treatment. Half of respondents report "always" in terms of frequency that contraception is addressed among their high-risk patients. After adjustment for gender, we found that the odds of reporting providing fertility counseling were nearly three times higher among attendings as compared to fellows [AOR = 2.72; 95% CI = (1.44, 5.12), three times higher in women as compared to men [AOR = 2.80; 95% CI = (1.46, 5.38)], as well as in individuals 50 + years as compared to those < 40 years old [AOR = 4.91; 95% CI = (2.05, 11.74)]. Ninety-six percent reported < 5 unplanned pregnancies, to their knowledge, in the previous five years of clinical practice. Most providers acknowledge that unplanned pregnancy is a potential risk in fertile gynecologic oncology patients, but only half believe their patients understand an unplanned pregnancy is possible. An opportunity exists to provide more directed counseling regarding fertility during and after cancer therapy, and to educate patients and providers regarding more reliable, long acting contraceptive methods.

Beyond Chemotherapy: An Overview and Review of Targeted Therapy in Cervical Cancer.

PURPOSE: The purpose of this study was to provide an overview of current and up and coming targeted therapies in cervical cancer with or without chemotherapy. METHODS: We reviewed the literature using search terms cervical cancer AND immunotherapy, immune therapy, vaccines, bevacizumab, anti-angiogenic therapy, and PARP inhibitors on PubMed. We included all review articles and prospective trials. We also reviewed ClinicalTrials.gov for trials in progress. FINDINGS: The addition of bevacizumab has improved the overall survival of women with advanced or recurrent cervical cancer when compared with cytotoxic therapy alone. This advancement has sparked an interest in other anti-angiogenic agents. Additionally, targeted therapies, including tyrosine kinase inhibitors, immunotherapy, and vaccine therapy, are also being evaluated. Another exciting area of study is the role of poly (ADP-ribose) polymerase inhibition in cervical cancer. IMPLICATIONS: Though the results are promising, the data are preliminary and additional studies evaluating the proper combination of therapy, dosing, and schedules will help inform the ideal regimen.