Oncologic therapy including chemotherapy and radiation can have a significant impact on ovarian function for young women and girls. Poor health outcomes and loss of fertility are major ...considerations. The effect of radiation and chemotherapy on ovarian function varies depending on patient age, therapy type and dosage, and cancer type. Surgical and medical interventions are available to reduce the morbidity of premature ovarian failure associated with cancer-directed therapy. Fertility preservation is an important consideration, and several options are available for it; therefore, early consultation with a reproductive or oncofertility specialist is an essential part of oncologic care in young women or girls. This chapter will focus on the effects of radiation and chemotherapy on ovarian function and strategies to improve the reproductive care in women with cancer.
•Premature ovarian failure and infertility may be indirect impacts of cancer and cancer therapies.•Strategies to reduce the impact of therapy on ovarian function should be offered when appropriate.•Multidisciplinary care with oncofertility consultation should be offered.
To determine the feasibility of hospital-based genetic counseling and testing (GC/T) Traceback for Ovarian Cancer (OC) patients, as proposed by the Division of Cancer Prevention and the Division of ...Cancer Control and Population Sciences, National Cancer Institute.
Living patients with OC were sent a letter explaining the availability of guideline-supported GC/T for at least BRCA1/2 and surrogates of deceased patients were called on the telephone. Outcomes of contact attempts were systematically recorded and statistically described.
598 Traceback-eligible OC patients diagnosed from 2006 to 2016 were identified (163 presumed-living and 435 deceased). Two living patients called our office and scheduled an appointment for GC/T after receiving a letter. For surrogates of prior patients, successful contact occurred in 25% of call attempts. Fourteen individuals (2 living patients and 12 surrogates) underwent genetic counseling. Of those 14, 10 individuals consented to genetic testing and 5 followed through with sample collection. None of these individuals had pathogenic variants (PVs). When surrogate call notes were reviewed, 58% reflected positive responses to contact, however 42% were noted to have negative or indifferent responses, which were most common among spouses. Total time spent for hospital-based Traceback was 109 h.
Overall, hospital-based Traceback via letter and telephone contact of surrogates is time-intensive and results in minimal uptake of GC/T. To practically execute this type of outreach program, health systems should consider collection of alternative contact information to allow for electronic communication of patient surrogates. Our study also underscores the importance of timely GC/T while patients are in active cancer care.
•Hospital-based Traceback results in minimal uptake of genetic counseling and genetic testing services.•Hospital-based Traceback is time intensive and may burden an already busy clinical practice.•Biological relatives were more likely than unrelated contact persons to respond positively to telephone contact.•Offering genetic counseling and testing services during active oncology may be the most effective strategy to ensure uptake.
Background
The objective of this study was to assess the correlation between mismatch repair (MMR) status, disease recurrence patterns, and recurrence‐free survival (RFS) in patients with ...high‐intermediate–risk (HIR) endometrioid endometrial cancer (EEC).
Methods
A single‐institution chart review for consecutive patients who were diagnosed with ECC between 2007 and 2016 was undertaken. Tumor MMR status was determined for all patients based on reported findings for mutL homolog 1 (MLH1), postmeiotic segregation (PMS2), mutS homolog 2 (MSH2), and MSH6 immunohistochemistry; and defective MMR (dMMR) status was defined as the lack of expression of at least 1 of these proteins. Patients were classified with HIR EEC according to criteria used for Gynecologic Oncology Group study 249. The factors associated with recurrence were assessed by logistic regression. RFS and associated factors were assessed by Kaplan‐Meier survival analysis and Cox proportional‐hazards models.
Results
In total, 197 patients who had HIR EEC (64 with dMMR and 133 with intact MMR iMMR) were identified, of whom 32 (16.2%) developed recurrent disease. The median follow‐up was 54 months. The recurrence rate for women who had dMMR was 28% compared with 10.5% for those who had iMMR (P = .002), independent of the type of adjuvant therapy they received. The increase in distant recurrences among patients who had dMMR was even more pronounced (14.1% vs 3%; P = .003). The estimated 5‐year RFS was 66% for women who had dMMR compared with 89% for those who had iMMR (P = .001). Excluding isolated vaginal recurrences, the difference in 5‐year RFS was 73.5% versus 95%, respectively (P = .0004).
Conclusions
Patients who had HIR EEC with dMMR had increased rates of recurrence and decreased RFS compared with those who had HIR EEC with iMMR, despite the receipt of similar adjuvant treatment. The current findings highlight the need for alternative treatment options and the importance of MMR status as a biomarker for patients with HIR EEC.
Patients who have high‐intermediate–risk endometrioid endometrial cancer with defective mismatch repair have increased rates of recurrence and decreased recurrence‐free survival compared with those who have high‐intermediate–risk disease with intact mismatch repair, despite the receipt of similar adjuvant treatment.
To evaluate the prognostic impact of aortic vs. pelvic lymph node (LN) metastasis among women with endometrial cancer (EC).
Using data from the SEER 18 Registries we identified 3650 women with LN ...positive (stage IIIC) EC. We used Kaplan-Meier curves and log-rank tests to compare mortality between women with stage IIIC1 and IIIC2 disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between stage III sub-stage (IIIC1 vs. IIIC2) and survival.
Endometrioid tumors were more common among women with stage IIIC1 than IIIC2 tumors (62.5% vs. 54.3%) while, non-endometrioid histologies were more common among stage IIIC2. In the multivariable model, stage IIIC2 was associated with higher all-cause (HR = 1.44, 95% CI = 1.22–1.69) and EC-specific mortality (HR = 1.49, 95% CI = 1.25–1.77) compared with IIIC1. Women with non-endometrioid EC had poor survival, in particular, women with carcinosarcomas had higher EC-specific mortality compared to women with endometrioid EC (HR = 3.32, 95% CI = 2.71–4.07). When stratifying women according to substage, older age and non-endometrioid histology were associated with higher EC-specific mortality. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower all-cause (HR = 0.74, 95% CI = 0.63–0.88) and EC-specific (HR = 0.79, 95% CI = 0.66–0.95) mortality.
Women with aortic LN positive EC are more likely to die from their disease. Older women and non-endometrioid histologies are more likely to have aortic LN involvement. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.
•Endometrial cancer with aortic lymph node metastasis portends a worse outcome.•Older age and non-endometrioid histology are independent poor prognostic indicators in lymph node positive EC.•Carcinosarcoma histology has the worse outcomes in lymph node positive EC.•Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.
Purpose
Endometrial cancer (EC) is the most common gynecological cancer among women in the United States. Despite well-documented racial/ethnic disparities in EC incidence and mortality rates, ...limited data exist regarding disparities in hysterectomy surgical outcomes. We evaluated associations of race/ethnicity with postoperative complications, serious adverse events (SAEs), and length of hospital stay among women undergoing EC-related hysterectomy.
Methods
Using National Surgical Quality Improvement Program (NSQIP) data, we identified women (≥18 years) undergoing hysterectomy to treat EC between 2014 and 2020. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of race/ethnicity (white, black, and Latina) with postoperative complications and SAEs. We used Poisson regression with robust standard errors to calculate incidence rate ratios (IRRs) and 95% CIs for the association of race/ethnicity with length of hospital stay.
Results
Of 22,778 women undergoing EC-related hysterectomy, 3.1% developed postoperative complications. Black (adjusted OR: 1.62; 95% CI 1.05–2.48) and Latina women (adjusted OR: 1.79; 95% CI 1.04–3.09) had higher postoperative complication risks than white women. The overall SAE incidence was 5.0%. Black women (adjusted OR: 1.55, 95% CI 1.13–2.15) had higher SAE risks than white women. Length of hospital stay was significantly longer for black women than white women (IRR: 1.18; 95% CI 1.07–1.30).
Conclusions
We observed racial/ethnic disparities in EC-related hysterectomy surgical outcomes in a large, diverse sample of U.S. women between 2014 and 2020. Studies to elucidate the underlying mechanisms of these racial disparities, with a focus on social context remain necessary.
We sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population.
Retrospective review of patients who ...underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test.
Eighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10–16 months), and median overall survival (OS) was 38 months (95% CI 19–61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550).
Stage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients.
•FIGO stage IVB endometrial cancer comprises a heterogenous patient population with varying outcomes.•Cytoreduction degree and pelvic-confined disease are prognostic; distant metastases are not associated with worse survival.•Patients who were down-staged following application of the new FIGO 2023 staging criteria had improved survival.•Future conversations are needed regarding contemporary surgical staging and role of lymphadenectomy for advanced disease.
•MLH1 methylated endometrial tumors have poor prognostic features including larger size.•Tumor volume and mismatch repair class are associated with lymph node involvement.•Women with MLH1 methylated ...tumors have reduced recurrence-free survival.•Recurrence rate by MMR class differed dramatically in advanced stage endometrial cancer.•MMR defective tumors with MLH1 methylation may exhibit chemoresistance.
To determine the relationship between mismatch repair (MMR) classification and clinicopathologic features including tumor volume, and explore outcomes by MMR class in a contemporary cohort.
Single institution cohort evaluating MMR classification for endometrial cancers (EC). MMR immunohistochemistry (IHC)±microsatellite instability (MSI) testing and reflex MLH1 methylation testing was performed. Tumors with MMR abnormalities by IHC or MSI and MLH1 methylation were classified as epigenetic MMR deficiency while those without MLH1 methylation were classified as probable MMR mutations. Clinicopathologic characteristics were analyzed.
466 endometrial cancers were classified; 75% as MMR proficient, 20% epigenetic MMR defects, and 5% as probable MMR mutations. Epigenetic MMR defects were associated with advanced stage, higher grade, presence of lymphovascular space invasion, and older age. MMR class was significantly associated with tumor volume, an association not previously reported. The epigenetic MMR defect tumors median volume was 10,220mm3 compared to 3321mm3 and 2,846mm3, for MMR proficient and probable MMR mutations respectively (P<0.0001). Higher tumor volume was associated with lymph node involvement. Endometrioid EC cases with epigenetic MMR defects had significantly reduced recurrence-free survival (RFS). Among advanced stage (III/IV) endometrioid EC the epigenetic MMR defect group was more likely to recur compared to the MMR proficient group (47.7% vs 3.4%) despite receiving similar adjuvant therapy. In contrast, there was no difference in the number of early stage recurrences for the different MMR classes.
MMR testing that includes MLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS.
The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome ...screening and molecular risk stratification.
Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods.
Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53–3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10–7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04–4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status.
A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system.
•Molecular classification of endometrioid endometrial cancers identifies cases at increased risk for recurrence.•Women whose tumors have copy number alterations have reduced progression-free and cancer-specific survival.•~8% of endometrioid endometrial cancers are copy number altered, the majority of which are low grade, low stage cases.
Purpose of Review
This article will discuss the recent data on the prognostic significance of molecular classification of endometrial carcinoma, as well as its impact on directing treatment ...decisions.
Recent Findings
Molecular classification has emerged as a complement to the current paradigm of endometrial cancer (EC) risk stratification.
POLE
mutations appear to portend favorable prognoses, but data are insufficient to indicate withholding treatment based on this signature. Copy number high (CNH) EC carries a worse prognosis and may benefit from more aggressive therapy. MMRd tumors are likely to have other prognostic features that indicate adjuvant treatment and many recurrences respond favorably to pembrolizumab. Progression of molecular profiling may allow further discrimination of the no specific molecular profile (NSMP) group. Treatment for this group remains largely based on conventional risk factors. For both the NSMP and the CNH groups, treatment with lenvatinib and pembrolizumab is an attractive contemporary option for recurrence management.
Summary
Molecular classification is a useful adjunct to conventional risk stratification paradigms for both prognostic counseling and treatment selection. Clinical trials incorporating molecular signatures in assigning treatment strategies may further elucidate the value of this classification system.
PDF
