Journal of the National Comprehensive Cancer Network

Racial and Ethnic Disparities in the Time to Ovarian Cancer Surgery in Patients at an Integrated Health Care Delivery System

Background: Disparities in ovarian cancer survival for African American women are multifactorial. We evaluated racial and ethnic differences in time to ovarian cancer surgery in members of an integrated health care system. Patients and Methods: In this retrospective cohort study, we identified women diagnosed with invasive epithelial-type ovarian cancer between January 1, 2008, through December 31, 2014, at an integrated health care system in the United States. We extracted data on cancer-related variables and sociodemographic variables from the health care system’s cancer registry and electronic health records. We included patients who received ovarian cancer surgery without neoadjuvant chemotherapy. We defined time to surgery as the number of days between diagnostic imaging study and surgery. We used Cox proportional hazards regression to evaluate crude and adjusted association of race and ethnicity with time to surgery. Results: Of 872 patients included, 55.1% were non-Hispanic White (hereafter, White), 24.9% were Hispanic, 14.6% were Asian/Pacific Islander (PI)/Native American, and 5.5% were African American. Median age at diagnosis was 59.0 years. African American patients were diagnosed at an older age and were more likely to come from deprived neighborhoods than other racial and ethnic groups. Median time to surgery was longer for African American patients compared with White, Hispanic, and Asian/PI/Native American patients (median days: 27.5 vs 21.0, 24.5, and 26.0, respectively; P<.0001). In adjusted models, the likelihood of having received surgery at any given time post diagnostic imaging was 31% lower for African American patients compared with White patients (HR, 0.69; 95% CI, 0.51–0.93). This likelihood was also lower for Hispanic and Asian/PI/Native American patients, but not statistically significant. Conclusions: Our findings showed that patients with ovarian cancer from racial and ethnic minorities had a lower likelihood of having received surgery at any given time post diagnostic imaging compared with White patients, demonstrating that racial and ethnic differences exist in time to ovarian cancer surgery in patients with relatively equal access to care.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer

Background: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)–based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. Methods: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. Results: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year’s testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. Conclusions: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Locally Advanced Cervical Cancer: What is the Preferred Systemic Treatment?

Cervical cancer remains the fourth most common malignancy among women globally and is a leading cause of cancer mortality. For patients with locally advanced cervical cancer (LACC), the established standard of care is definitive treatment with concurrent cisplatin therapy and external-beam radiation therapy (chemoradiotherapy [CRT]) followed by brachytherapy. Although treatment with CRT is potentially curative, recent studies have shown the 5-year overall survival rate for patients with LACC is approximately 74%. The role of additional systemic chemotherapy or immunotherapy has been investigated in prospective randomized controlled trials, and recently published results suggest the benefit of alternative regimens. This review discusses the history of treatment with concurrent cisplatin-based CRT and examines data on consolidation chemotherapy, induction chemotherapy, and immunotherapy in LACC.

Cervical Cancer, Version 2.2026, NCCN Clinical Practice Guidelines In Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer provide diagnostic workup, staging, and various treatment recommendations for cervical cancer based on clinical and surgical staging. This selection from the NCCN Guidelines for cervical cancer specifically focuses on diagnosis and workup, principles of staging and surgery, and primary treatment recommendations for early-stage and advanced disease and provides a detailed overview of systemic therapy recommendations for cervical cancer.

Evaluation of Scores to Reflect Toxicity Impact on Quality of Life of Patients With Platinum-Resistant Ovarian Cancer: AURELIA Substudy

Background: Current standards for toxicity reporting do not fully capture the impact of adverse events (AEs) on patients’ quality of life (QoL). This study aimed to evaluate the association between toxicity and QoL by using toxicity scores that take into account CTCAE grade grouping and AE duration and cumulation. Methods: Analyses were performed on the AURELIA trial dataset, including 361 patients with platinum-resistant ovarian cancer treated with chemotherapy alone or with bevacizumab. Global and physical functioning QoL were issued from the EORTC QoL Questionnaire-Core 30 (QLQ-C30), collected at baseline and 8/9 and 16/18 weeks after treatment initiation. Four toxicity scores were computed: the total number of AEs, multiplied by their grade and not, and the cumulative duration of AEs, weighted by their grade and not. Each score included all AEs or only grade 3/4 nonlaboratory or treatment-related AEs. The relationship between toxicity scores and QoL was assessed through linear mixed regression. Results: We found that 171 (47.5%) and 43 (11.9%) patients experienced at least one grade 3 or 4 AE, respectively, whereas 113 (31.4%) experienced grade 2 AEs only. Physical QoL was negatively associated with all toxicity scores when computed with all grades of AEs (all P<.01), with a weaker association when treatment-related AEs were considered. Global QoL was negatively associated with toxicity scores computed with nonlaboratory all-grade AEs only (β, –3.42 to –3.13; all P<.01). Degrees of association were lower when considering the AE duration. Conclusions: In this analysis of patients with platinum-resistant ovarian cancer, toxicity scores based on the cumulative number of AEs, modulated or not by grade, were more effective at predicting QoL changes than those based on AE duration. Toxicity impact on QoL was better reflected when grade 2 AEs were taken into account together with grade 3/4 AEs, whatever their treatment imputability, and when laboratory AEs were excluded.

Nationwide Trends and Determinants of Germline BRCA1/2 Testing in Patients With Breast and Ovarian Cancer

Background: Germline genetic testing (GT) for BRCA1/2 is instrumental in identifying patients with breast and ovarian cancers who are eligible for PARP inhibitors (PARPi). Little is known about recent trends and determinants of GT since PARPi were approved for these patients. Patients and Methods: We performed a retrospective cohort study of patients in a nationwide electronic health record (EHR)–derived oncology-specific database with the following GT eligibility criteria: breast cancer diagnosed at age ≤45 years, triple-negative breast cancer diagnosed at age ≤60 years, male breast cancer, or ovarian cancer. GT within 1 year of diagnosis was assessed and stratified by tumor type. Multivariable log-binomial regressions estimated adjusted relative risks (RRs) of GT by patient and tumor characteristics. Results: Among 2,982 eligible patients with breast cancer, 56.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.08; 95% CI, 1.05–1.11, for each year), independent of when PARPi were approved for BRCA1/2-mutated metastatic breast cancer in January 2018. In multivariable analyses, older age (RR, 0.93; 95% CI, 0.90–0.96, for every 5 years) and Medicare coverage (RR, 0.69; 95% CI, 0.49–0.96 vs commercial insurance) were associated with less GT. Among 5,563 eligible patients with ovarian cancer, 35.4% underwent GT between January 2011 and March 2020, with a significant increase in GT over time (RR, 1.11; 95% CI, 1.07–1.14, for each year) that accelerated after approval of PARPi for BRCA1/2-mutated, chemotherapy-refractory ovarian cancer in December 2014 (RR, 1.42; 95% CI, 1.19–1.70). Older age (RR, 0.95; 95% CI, 0.93–0.97, for every 5 years) and Black or African American race (RR, 0.80; 95% CI, 0.65–0.98 vs White race) were associated with less GT. Conclusions: GT remains underutilized nationwide among patients with breast and ovarian cancers. Although GT has increased over time, significant disparities by age, race, and insurance status persist. Additional work is needed to design, implement, and evaluate strategies to ensure that all eligible patients receive GT.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Cost-Effectiveness of Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Background: Maintenance therapy with the PARP inhibitor olaparib for metastatic pancreatic cancer (MPC) with a germline BRCA1 or BRCA2 mutation has been shown to be effective. We aimed to evaluate the cost-effectiveness of maintenance olaparib for MPC from the US payer perspective. Materials and Methods: A partitioned survival model was adopted to project the disease course of MPC. Efficacy and toxicity data were gathered from the Pancreas Cancer Olaparib Ongoing (POLO) trial. Transition probabilities were estimated from the reported survival probabilities in each POLO group. Cost and health preference data were derived from the literature. The incremental cost-utility ratio, incremental net-health benefit, and incremental monetary benefit were measured. Subgroup analysis, one-way analysis, and probabilistic sensitivity analysis were performed to explore the model uncertainties. Results: Maintenance olaparib had an incremental cost-utility ratio of $191,596 per additional progression-free survival (PFS) quality-adjusted life-year (QALY) gained, with a high cost of $132,287 and 0.691 PFS QALY gained, compared with results for a placebo. Subgroup analysis indicated that maintenance olaparib achieved at least a 16.8% probability of cost-effectiveness at the threshold of $200,000/QALY. One-way sensitivity analyses revealed that the results were sensitive to the hazard ratio of PFS and the cost of olaparib. When overall survival was considered, maintenance olaparib had an incremental cost-utility ratio of $265,290 per additional QALY gained, with a high cost of $128,266 and 0.483 QALY gained, compared with results for a placebo. Conclusions: Maintenance olaparib is potentially cost-effective compared with placebo for patients with a germline BRCA mutation and MPC. Economic outcomes could be improved by tailoring treatment based on individual patient factors.

Adjuvant Treatment of Early Ovarian Clear Cell Carcinoma: A Population-Based Study of Whole Abdominal Versus Pelvic Nodal Radiotherapy

Background: Adjuvant treatment in early ovarian clear cell carcinoma (OCCC) is not yet standardized. The objective of this population-based study was to compare the outcome of patients with early OCCC treated with adjuvant chemotherapy versus chemoradiotherapy (chemoRT) and evaluate the association of adjuvant radiotherapy regimens (whole abdominal radiotherapy [WART] versus pelvic nodal radiotherapy [PRT]) with outcome. Patients and Methods: Chart review was conducted to identify patients with stage I and II OCCC with complete information on staging. Patients with stage IA, IB, or IC OCCC purely resulting from capsular rupture were excluded because the provincial protocol does not recommend adjuvant treatment. Results: Overall, 403 patients were identified and 343 received adjuvant treatment, of whom 255 had stage IC or II OCCC and 153 were eligible for final analysis. On Cox multivariable regression, receipt of chemoRT (n=90) was associated with an improvement in failure-free survival (FFS) (hazard ratio [HR], 0.57; 95% CI, 0.34–0.94) compared with chemotherapy alone (n=63). Use of chemoRT also resulted in 54% reduction in the cumulative incidence of cancer-specific mortality (subdistribution HR, 0.46; 95% CI, 0.24–0.89). However, there was no significant difference in the HR for overall survival (OS) between the chemoRT (HR, 0.70; 95% CI, 0.43–1.13) and chemotherapy group. Relative to chemotherapy + WART (chemo-WART), chemotherapy + PRT (chemo-PRT) was not associated with any significant difference in HR for FFS (HR, 1.34; 95% CI, 0.40–4.44) or OS (HR, 1.13; 95% CI, 0.37–3.46). Conclusions: Adjuvant chemoRT was associated with a lower risk of failure compared with chemotherapy alone. However, there was no difference in OS between the adjuvant chemotherapy and chemoRT regimens. Additionally, no significant difference in terms of FFS or OS was found between the chemo-WART and chemo-PRT groups.

PTCH1-GLI1 Fusion–Positive Ovarian Tumor: Report of a Unique Case With Response to Tyrosine Kinase Inhibitor Pazopanib

Recurrent GLI1 gene fusions have been recently described in a subset of soft tissue tumors showing a distinct monotonous epithelioid morphology with a rich capillary network and frequent S100 protein expression. Three different fusion partners—ACTB, MALAT1, and PTCH1—have been reported with the PTCH1-GLI1 fusion from 2 patients only, both with head and neck tumors. Herein, we report for the first time a PTCH1-GLI1 fusion in a primary ovarian tumor from a female patient aged 54 years who presented with a 21-cm right ovarian mass and mesenteric metastasis. The tumor was diagnosed as “favor malignant melanoma” based on histologic examination and extensive immunohistochemistry studies. The patient received 4 cycles of pembrolizumab and 2 cycles of trabectedin but developed multiple metastases. A next-generation sequencing-based assay detected a PTCH1-GLI1 fusion, which led to a revised pathologic diagnosis and a change of the patient’s management. The patient was switched to the tyrosine kinase inhibitor (TKI) pazopanib to target the sonic hedgehog pathway. Her disease was stable 49 months post TKI therapy. Our case report is the first to show that a tumor with GLI1 oncogenic activation was sensitive to a TKI. The morphologic and immunohistochemistry similarities of our patient’s tumor to other recently described tumors harboring GLI1 fusions suggest that these tumors may all belong to the same entity of GLI1 fusion–positive neoplasms and may be treated similarly.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.

Exceptional Response to Olaparib in a Patient With Recurrent Ovarian Cancer and an Entire BRCA1 Germline Gene Deletion

PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes (BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for >3 years on olaparib, with an overall survival of >12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells’ inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.

BPI26-008: Optimizing Germline Genetic Referral and Testing Rates for High-Grade Serous Ovarian Cancer Patients

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

Healthcare Access Dimensions and Guideline-Concordant Ovarian Cancer Treatment: SEER-Medicare Analysis of the ORCHiD Study

Background: Racial disparities exist in receipt of guideline-concordant treatment of ovarian cancer (OC). However, few studies have evaluated how various dimensions of healthcare access (HCA) contribute to these disparities. Methods: We analyzed data from non-Hispanic (NH)–Black, Hispanic, and NH-White patients with OC diagnosed in 2008 to 2015 from the SEER-Medicare database and defined HCA dimensions as affordability, availability, and accessibility, measured as aggregate scores created with factor analysis. Receipt of guideline-concordant OC surgery and chemotherapy was defined based on the NCCN Guidelines for Ovarian Cancer. Multivariable-adjusted modified Poisson regression models were used to assess the relative risk (RR) for guideline-concordant treatment in relation to HCA. Results: The study cohort included 5,632 patients: 6% NH-Black, 6% Hispanic, and 88% NH-White. Only 23.8% of NH-White patients received guideline-concordant surgery and the full cycles of chemotherapy versus 14.2% of NH-Black patients. Higher affordability (RR, 1.05; 95% CI, 1.01–1.08) and availability (RR, 1.06; 95% CI, 1.02–1.10) were associated with receipt of guideline-concordant surgery, whereas higher affordability was associated with initiation of systemic therapy (hazard ratio, 1.09; 95% CI, 1.05–1.13). After adjusting for all 3 HCA scores and demographic and clinical characteristics, NH-Black patients remained less likely than NH-White patients to initiate systemic therapy (hazard ratio, 0.86; 95% CI, 0.75–0.99). Conclusions: Multiple HCA dimensions predict receipt of guideline-concordant treatment but do not fully explain racial disparities among patients with OC. Acceptability and accommodation are 2 additional HCA dimensions which may be critical to addressing these disparities.

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country’s fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Race- and Age-Related Disparities in Cervical Cancer Mortality

Background: Although the incidence of cervical cancer among younger Black women is now equivalent to that of White women, it is unknown whether the reduced incidence has affected survival rates among younger Black women. The goal of this study was to assess differences in survival by age and race. Patients and Methods: A retrospective cohort study was performed using the National Cancer Database to analyze women with nonmetastatic cervical cancer diagnosed between 2004 and 2014. Women with unknown survival data and those who died within 3 months of diagnosis were excluded. Multivariable logistic regression models evaluated interactions between age and race (Black vs non-Black) for presentation with stage I disease and receipt of optimal treatment. A multivariable Cox regression model was used to evaluate survival differences by age and race. Results: Of 55,659 women included, 16.4% were Black. Compared with their non-Black counterparts, fewer Black women presented with stage I disease (37.8% vs 47.8%; P<.01) and received optimal treatment (46.2% vs 58.3%; P<.01). Fewer Black women had private insurance if they were aged <65 years (39.6% vs 55.7%; P<.01), but not if they were aged ≥65 years (11.7% vs 12.4%; P=.43). According to multivariable logistic regression, Black women aged ≤39 years were less likely to present with stage I disease, with a significant interaction term between age and race (P<.01 for interaction). Disparities in overall survival by race were greatest for Black women aged ≤39 years (adjusted hazard ratio, 1.32; 95% CI, 1.20–1.46; P<.01) but decreased with increasing age interval until no disparity was noted for women aged ≥65 years (P<.01 for interaction). Conclusions: Younger Black women with cervical cancer are at risk for presenting with higher-stage disease and having worse overall survival. These findings may be related to insurance-related disparities and inadequate follow-up for abnormal Papanicolaou test results. Younger Black women with cervical cancer may be a particularly vulnerable population.

Reducing Disparities in Cervical Cancer Mortality Among Young Black Women

Patterns and Trends of Cancer Screening in Canada: Results From a Contemporary National Survey

Background: The aim of this study was to assess the patterns and trends of colorectal, breast, and cervical cancer screening within a contemporary cohort of Canadian adults. Methods: Canadian Community Health Survey datasets (2007–2016) were accessed and 3 cohorts were defined: (1) a colorectal cancer (CRC) screening cohort, defined as men and women aged 50 to 74 years with complete information about CRC screening tests and their timing; (2) a breast cancer screening cohort, defined as women aged 40 to 74 years with complete information about mammography and its timing; and (3) a cervical cancer screening cohort, defined as women aged 25 to 69 years with complete information about the Papanicolaou (Pap) test and its timing. Multivariable logistic regression analysis was then performed to evaluate factors associated with not having timely screening tests at the time of survey completion. Results: A total of 99,820 participants were considered eligible for the CRC screening cohort, 59,724 for the breast cancer screening cohort, and 46,767 for the cervical cancer screening cohort. Among eligible participants, 43% did not have timely recommended screening tests for CRC, 35% did not have timely mammography (this number decreased to 26% when limiting the eligible group to ages 50–74 years), and 25% did not have a timely Pap test. Lower income was associated with not having a timely recommended screening tests for all 3 cohorts (odds ratios [95% CI]: 1.86 [1.76–1.97], 1.89 [1.76–2.04], and 1.96 [1.79–2.14], respectively). Likewise, persons self-identifying as a visible minority were less likely to have timely recommended screening tests in all 3 cohorts (odds ratios for White race vs visible minority [95% CI]: 0.87 [0.83–0.92], 0.85 [0.80–0.91], and 0.66 [0.61–0.70], respectively). Conclusions: More than one-third of eligible individuals are missing timely screening tests for CRC. Moreover, at least one-quarter of eligible women are missing their recommended breast and cervical cancer screening tests. More efforts from federal and provincial health authorities are needed to deal with socioeconomic disparities in access to cancer screening.

Extended HPV Genotyping for Risk Assessment of Cervical Intraepithelial Neoplasia Grade 2/3 or Worse in a Cohort Study

Background: We sought to identify the absolute risk of specific HPV genotype for cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/3+) and to develop a risk-based management strategy in an HPV-positive population. Methods: HPV genotyping was performed based on a 3-year cervical cancer screening cohort. The study endpoints were histologic CIN2+/3+. The prevalence of specific HPV genotype was calculated by minimum, any type, and hierarchical attribution estimate. The absolute CIN2+/3+ risks of specific HPV genotype were estimated and risk-based management strategy was established according to the American Society for Colposcopy and Cervical Pathology guideline. The efficacy of conventional and risk-based management strategies for non-16/18 HPVs were further evaluated. Results: Eligible data were available for 8,370 women with a median age of 48 years (interquartile range, 42–53 years). At baseline, there were 1,062 women with HPV-positive disease, including 424 with multiple and 639 with single infections. CIN2+/3+ cases represented 113/74, 23/8, 20/7, and 52/31 patients at baseline and first-, second-, and third-year visits, respectively. Women with multiple HPV infections at baseline were more prone to persistent infection than those with single infection (P<.0001). HPV16 and HPV52 were the top 2 ranking among baseline and 3-year cumulative CIN2+/3+ cases. Based on the absolute risk of specific HPV genotype combined with cytology for CIN2+/3+, all non-16/18 HPVs were divided into 4 risk-stratified groups. Compared with conventional strategy, the risk-based strategy had higher specificity (P=.0000) and positive predictive value (P=.0322) to detect CIN3+ and needed fewer colposcopies for each CIN3+ case. Conclusions: Based on our study findings, we propose a new extended HPV genotyping protocol, which would provide a better strategy for achieving precise risk-based management of HPV-positive populations.

Ovarian Function Suppression in HR-Positive, HER2-Positive Breast Cancer: An Exploratory Analysis of the HERA Trial

Background: Data on the effectiveness of ovarian function suppression (OFS) in premenopausal patients with hormone receptor (HR)–positive, HER2-positive breast cancer are sparse. We investigated the prognostic impact of incorporating OFS in premenopausal women with HER-positive, HR-positive breast cancer, drawing on data from the HERceptin Adjuvant (HERA) trial. Patients and Methods: We examined patient-level data from the HERA trial (BIG1-01) to assess whether adding OFS enhances disease-free survival (DFS) and overall survival (OS) in premenopausal women with early-stage HR-positive, HER2-positive breast cancer. Additionally, we explored differences in prognosis between types of oral antiestrogens, specifically tamoxifen (TAM) and aromatase inhibitors (AIs). Results: A total of 965 patients were included in our analysis; 501 (51.9%) received TAM only, and 464 (48.1%) underwent endocrine therapy with OFS. The addition of OFS independently correlated with enhanced DFS (hazard ratio, 0.68; 95% CI, 0.53–0.87; P =.002) and OS (hazard ratio, 0.62; 95% CI, 0.44–0.85; P =.003). The 10-year DFS rates were 70.9% with OFS versus 59.6% with TAM only, whereas the 10-year OS rates were 84.7% with OFS versus 74.0% with TAM only. Among the patients treated with OFS, AI was associated with favorable survival outcomes compared with TAM. Conclusions: Our findings suggest that adding OFS to adjuvant endocrine therapy may improve survival outcomes in premenopausal women with HR-positive, HER2-positive breast cancer who are receiving chemotherapy and HER2-targeted therapy, and are at high risk of relapse. ClinicalTrials.gov identifier: NCT00045032

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, Version 2.2026

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

Molecular Profiling of Endometrial Cancer From TCGA to Clinical Practice

Molecular classification provides an objective, reproducible framework for categorization of endometrial cancers (ECs), informing prognosis and selection of therapy. Currently, the uptake of molecular classification, integration in to EC management algorithms, and enrollment in molecular subtype-specific clinical trials lags behind what it could be. Access to molecular testing is not uniform, and subsequent management (surgical, adjuvant therapy) is unacceptably variable. We are in the midst of a critical landscape change in this disease site, with increasing emphasis on the integration of molecular features in EC care that can potentially improve standard of care globally. This article summarizes the rationale for molecular classification of ECs, strategies for implementation in low and high resource settings, and actionable opportunities based on this information.

Optimizing Ovarian Cancer Treatment and Prevention Through Parallel Germline and Somatic Genetic Testing

NCCN Guidelines® Insights: Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, Version 3.2024

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.

Germline PALB2 Variants and PARP Inhibitors in Endometrial Cancer

PARP inhibitors are orally administered antineoplastic agents that affect the homologous recombination (HR) repair pathway, and are approved by the FDA for the treatment of ovarian, breast, pancreatic, and prostate cancers. This report presents a case of recurrent endometrial carcinoma occurring in a woman with a germline pathogenic PALB2 whole-exon deletion. This uncommon finding in a patient with endometrial carcinoma provided the opportunity to use a management strategy of PARP inhibition with olaparib, resulting in a prolonged response to treatment; however, disease progression eventually occurred. Further studies are required to elucidate the mechanisms underlying resistance to PARP inhibition, and the potential future treatment options in this setting. Current recommendations for risk management of female carriers of PALB2 variants focus on breast and ovarian cancer risk. This case raises the additional question of a potential role for risk-reducing hysterectomy in female carriers of PALB2 variants.

Impact of the Identification of Nonhuman Genetic Signatures in the Diagnosis and Management of Carcinoma of Unknown Primary

This report presents the case of a 62-year-old woman who was diagnosed in 1999 with stage I cervical carcinoma treated by surgical resection. In 2021, she presented to the emergency department with a complaint of predominantly right-sided lower back pain. A CT scan of the lumbosacral region revealed a bone lesion in the L5 vertebra and retroperitoneal lymphadenopathies suggestive of malignancy. Histology of the L5 vertebra biopsy showed a poorly differentiated carcinoma with an inconclusive immunophenotypic profile. Treatment for carcinoma of unknown primary was started with a combination of carboplatin and paclitaxel every 21 days. A genomic study of the biopsy specimen performed on the FoundationOne CDx platform identified a nonhuman genetic signature compatible with HPV. The presence of HPV 18 DNA in the specimen was confirmed by PCR-reverse dot blot, and the immunophenotypic profile was expanded, revealing strong and diffuse p16 expression, thus corroborating the molecular findings. In view of these findings, the case was reclassified as a recurrence of the cervical adenocarcinoma that had been diagnosed and treated 23 years earlier. Based on the new results, and according to first-line cervical carcinoma protocols, bevacizumab at 15 mg/kg every 21 days was added to her chemotherapy regimen. The identification of HPV DNA sequences by next-generation sequencing facilitated the correct diagnosis and led to a modification of the first-line therapeutic approach.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing. This manuscript also describes recent updates to these guidelines regarding de-implementation of colon cancer screening in individuals with CHEK2 pathogenic/likely pathogenic variants, based on the most up-to-date evidence regarding the association between CHEK2 pathogenic/likely pathogenic variants and colon cancer risk.

Impact of Provider Imaging Practices on Survival Outcomes in Advanced Ovarian Cancer

Background: This study sought to describe how high- versus low-frequency surveillance imaging practices among providers at Memorial Sloan Kettering Cancer Center (MSKCC) impact overall survival (OS) and time to recurrence of patients with advanced epithelial ovarian cancer in first remission. Methods: The study cohort included patients with stage II–IV high-grade epithelial ovarian cancer diagnosed in January 2001 through January 2017 who experienced recurrence after initial platinum-based chemotherapy. To determine usual imaging practices for providers at MSKCC, median frequency of CT or MRI of the abdomen/pelvis was calculated among patients with a long-term remission (defined as at least 1 year) treated by each provider. Cox proportional hazards models were used to examine differences in OS and time to recurrence among patients treated by providers with high versus low imaging frequency practices, with additional subgroup analysis among patients with elevated CA-125 levels >35 U/mL at diagnosis. Chi-square tests were used to examine differences in the proportion of patients who enrolled in clinical trials or underwent secondary cytoreductive surgery (SCS) by imaging frequency. Results: A total of 543 patients were treated by providers with high imaging frequency (>1 scan every 12 months) and 141 were treated by providers with low imaging frequency (≤1 scan every 12 months). Time to recurrence was shorter among patients treated by providers with high versus low imaging frequency (18.0 vs 19.2 months; hazard ratio, 1.33; P=.003). Results were similar when restricted to patients with elevated CA-125 levels at diagnosis. There was no significant difference in OS, clinical trial enrollment, or SCS by imaging practice. Conclusions: Within the limitations of this retrospective analysis, patients with advanced ovarian cancer treated by high-frequency-imaging providers had earlier detection of recurrence. Future analyses in a larger population are warranted to elucidate the risks versus benefits of surveillance imaging.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Modern Management of Newly Diagnosed Vulvovaginal Melanoma

Vulvovaginal melanomas are rare cancers of the vulva and vagina that are often treated similarly despite important differences. Furthermore, although these melanomas are generally considered mucosal, due to their rarity and limited clinical trial data and level I evidence they are often treated with cutaneous melanoma strategies. Resection of the tumor, with or without lymph node assessment, is the preferred primary treatment approach for these cancers. Breslow thickness is a main determinant of surgical approach, and a negative excision margin should be the goal, if possible, without pelvic exenteration. The advent of targeted therapies and immunotherapies has led to new standards in the adjuvant setting, with potential in the neoadjuvant setting as well; however, there is a strong need for mucosal and vulvovaginal melanoma–specific trials and data to guide treatment, and trial participation should be recommended for all patients with these cancers.

Modern Radiation Therapy Techniques for Vaginal Carcinoma

Definitive radiation therapy is the backbone of treatment in the management of primary vaginal cancer. The use of modern treatment techniques, such as intensity-modulated radiotherapy (RT) and image-guided adaptive brachytherapy, allows for the precise delivery of higher radiation doses to the tumor with reduced exposure to surrounding normal tissues compared with older, conventional 2D techniques. These advances in treatment planning have resulted in a nearly 10% absolute improvement in survival, along with a significant reduction in severe treatment-related toxicity. Accurate target volume delineation based on the tumor location and extent at presentation is crucial and is achieved with greater precision due to advances in imaging, including the routine incorporation of MRI into treatment planning. The brachytherapy target volume concepts used in the management of vaginal cancers largely mirror the adaptive approaches established for cervical cancers, incorporating tumor response following external-beam RT. Additionally, the expanding array of brachytherapy applicators, including both hybrid and custom options, has improved the ease and conformality of tumor implantation compared with standard template-based approaches. This review summarizes modern RT concepts and techniques in the management of primary vaginal cancer.

Vaginal Cancer, Version 2.2026, NCCN Clinical Practice Guidelines In Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Update on the Sentinel Node Procedure in Vulvar Cancer

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget’s disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2025

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer and uterine sarcoma. The NCCN Cervical Uterine Panel meets at least annually to review comments from reviewers within their institutions; examine relevant new data from publications, abstracts, and recent FDA approvals; and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s deliberations on the new FIGO 2023 staging system and updates on the new systemic therapy recommendations for the management of endometrial cancer.

Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.