To examine patients with confirmed endometrial cancer recurrence; evaluate patterns, presentation, and mode of diagnosis.
A retrospective review of women with endometrial cancer diagnosis between ...2014 and 2020. Disease recurrences were evaluated. Medical records were reviewed focusing on presentation at time of recurrence. Relationships were assessed using χ2, Fisher's exact test, t-test, and Wilcoxon test. The Kaplan-Meier product limit was used to estimate survival. Multiple logistic regression analysis was used to assess the impact of covariates.
Endometrial cancer recurrence was identified in 201 (11.7%) patients. Sixty percent (120/201) of patients presented with symptoms. Pain was the most common presenting symptom (23.4%, 47/201) and bleeding was reported in <14% (28/201). Patients with symptomatic presentation were less likely to be able to receive treatment for their recurrent disease (76.7% vs 91.3%, p = 0.005). Asymptomatic pelvic exam diagnosed recurrence in 13.4% (27/201) and was more common in patients initially diagnosed with early-stage disease (66.7% vs 34.5% p = 0.001) of endometrioid histology (66.7% vs 36.8%, p = 0.003) without prior adjuvant therapy (48.2% vs 17.9%, p = 0.001). More than1/3 of diagnoses were made by providers outside of the oncologic care team.
The majority of women with recurrent endometrial cancer were symptomatic and pain is a common complaint associated with disease recurrence. Patients with symptomatic presentation of disease recurrence were less likely to receive treatment for recurrent disease but this did not result in an overall survival (OS) difference. Given the rising mortality rate of endometrial cancer further work is needed to develop multidisciplinary surveillance strategies that will enable meaningful treatment of disease recurrence.
•The majority of endometrial cancer recurrences are symptomatic, and pain is the most common symptom.•Vaginal bleeding was reported in less than a quarter of symptomatic presentations.•More than a third of recurrences were diagnosed outside of the oncologic care team and frequently in the emergency room.•Seventeen percent of patients were unable to receive treatment for recurrent disease.
Background
Endometrial cancer (EC) is the most common gynecologic cancer in the U.S. The objective of this cohort study was to characterize the clinical and pathologic features that are associated ...with endometrial cancer–specific death for women cared for at a single National Cancer Institute–designated comprehensive cancer center.
Patients, Materials, and Methods
This is a retrospective cohort from 2014 to 2017 including all women who had a hysterectomy for EC. Charts were reviewed for clinical and pathologic data, focusing on survival outcomes.
Results
Seven hundred seventy‐one patients with EC underwent hysterectomy with 760 informative for outcomes. Seventy‐six (10%) deaths were related to their EC; 62 women died from recurrent EC. Nonendometrioid histology and advanced stage were predictors of recurrence and EC death. Among patients with endometrioid ECs, mismatch repair status was significantly associated with EC‐specific survival (relative risk = 4.8; 95% confidence interval, 2.3–10.3; p < .0001). Most patients with EC who recurred died of their disease 62/83 (74.7%). Nearly half of the patients that recurred (27/62) had no additional therapy at the time of recurrence. Overall survival was significantly longer for those women who had additional treatment at the time of recurrence; however, the improvement in overall survival with therapy at recurrence was largely attributable to effects in those women who were adjuvant therapy naïve.
Conclusion
Although there is benefit of treatment at the time of recurrence for treatment‐naïve women; only approximately half of patients were able to receive therapy. There is an urgent need for continued efforts for more effective EC therapy in both the front‐line and recurrent setting as well as early identification of cancer diagnosis and recurrence.
Implications for Practice
Approximately 10% of patients died of their endometrial cancer. Most deaths were from recurrent disease; however, almost 20% of endometrial cancer deaths were within 120 days of surgery. Although treatment at the time of recurrence improves overall survival, only approximately half of patients will receive therapy at the time of recurrence. Traditional prognostic features like histology and stage remain important to predict risk of recurrence, and newer biomarkers, such as mismatch repair status, may improve risk stratification and targeted therapy. There remains an urgent need for improved therapy and early detection of diagnosis and recurrence.
This article evaluates the clinical and pathologic data from a contemporary cohort of women who had a hysterectomy for endometrial cancer, to better understand factors that are associated with recurrences and deaths.
We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based ...chemotherapy (PC) for endometrial cancer (EC).
A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test.
Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25–3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01–4.18, p = 0.04).
In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients.
•Many patients will use antibiotics and/or a proton pump inhibitor at time of adjuvant therapy for endometrial cancer.•PPI use at time of adjuvant platinum-based chemotherapy is independently associated with worse outcomes.•Antibiotic use at time of adjuvant platinum-based chemotherapy was associated with worse survival on univariate analysis.
Mismatch repair (MMR) protein–deficient non-neoplastic colonic crypts and endometrial glands (dMMR crypts and glands) have been reported as a unique marker of underlying Lynch syndrome (LS). However, ...no large studies have directly compared the frequency of detection in cases with double somatic (DS) MMR mutations. We retrospectively analyzed 42 colonic resection specimens (24 LS and 18 DS) and 20 endometrial specimens (9 LS and 11 DS), including 19 hysterectomies and 1 biopsy for dMMR crypts and glands. All specimens were from patients with known primary cancers, including colonic adenocarcinomas and endometrial endometrioid carcinomas (including 2 mixed carcinomas). Four blocks of normal mucosa away from the tumor were selected from most cases, as available. MMR immunohistochemistry specific to the primary tumor mutations was analyzed. dMMR crypts were found in 65% of LS and 0% of DS MMR–mutated colonic adenocarcinomas (P < .001). Most dMMR crypts were detected in the colon (12 of 15) compared to the ileum (3 of 15). dMMR crypts showed single and grouped losses of MMR immunohistochemical expression. dMMR glands were found in 67% of LS and 9% (1 of 11) of DS endometrial cases (P = .017). Most dMMR glands were found in the uterine wall, with 1 LS and 1 DS case exhibiting dMMR glands in the lower uterine segment. Most cases exhibited multifocal and grouped dMMR glands. No morphologic atypia was identified in dMMR crypts or glands. Overall, we demonstrate that dMMR crypts and glands are highly associated with underlying LS, while being rarer in those with DS MMR mutations.
•Mismatch repair (MMR) –deficient non-neoplastic colonic crypts and endometrial glands are mostly found in Lynch syndrome.•Only one case of MMR-deficient non-neoplastic endometrial glands was detected which was due to double somatic MLH1 mutations).•No cases of MMR-deficient non-neoplastic colonic crypts have been identified in patients with double somatic MMR mutations.•Screening for MMR-deficient non-neoplastic colonic crypts and endometrial glands may provide guidance on patient management.
•Molecular classification of endometrial cancer is on the horizon.•The benefit of adjuvant therapy for women with POLE mutant endometrial cancers is uncertain.•Caution must be used in applying POLE ...data to clinical practice.
To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy.
Retrospective review was performed of ...patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 – August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests.
374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 1.14–4.11, p = 0.019) and surgical completion time after 12 PM (OR 3.67 2.16–6.24, p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted.
Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.
•Same day discharge following minimally invasive hysterectomy is generally safe and feasible for morbidly obese patients.•Age, BMI, medical co-morbidities, surgery time and frailty were associated with likelihood of undergoing same day discharge.•Routine overnight observation after minimally invasive hysterectomy led to little clinically meaningful intervention.•Hospital readmission rates are not higher for patients who undergo same day discharge.•A trend toward worse post-operative outcomes was seen in morbidly obese patients who met objective criteria for frailty.
To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor.
Clinical data and survival were compared between GCCC and more ...common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references.
143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease.
Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC.
GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.
•A National Cancer Database (NCDB) analysis shows worse outcomes for glassy cell carcinoma of the cervix across all stages.•When cases are staged by 2018 FIGO staging, outcomes are not worse for early-stage GCCC in the institutional series.
With the increasing rates of same-day discharge following minimally invasive surgery for endometrial cancer, the need for and value of routine postoperative testing is unclear.
This study aimed to ...determine whether routine postoperative laboratory testing following minimally invasive hysterectomy for endometrial cancer leads to clinically significant changes in postoperative care.
This was a single-institution retrospective cohort study of patients undergoing minimally invasive hysterectomy for endometrial cancer by a gynecologic oncologist between June 2014 and June 2017. Patient demographics, preoperative comorbidities, operative and postoperative data, and pathologic findings were manually extracted from the patients’ medical records. The financial burden of laboratory testing was computed using hospital-level cost data.
Of the 649 women included in the analysis, most (91.4%) were White, with a mean age of 61 years, and mean body mass index of 38.0 kg/m2. The most common comorbidities were diabetes mellitus (31.9%, n=207), chronic pulmonary disease (7.9%, n=51), and congestive heart failure (3.2%, n=21). Median operative time was 151 minutes (range, 61–278), and median estimated blood loss was 100 mL (range, 10–1500). Most patients (68.6%, n=445) underwent lymphadenectomy. All patients had postoperative laboratory tests ordered: 100% complete blood count, 99.7% chemistry, 62.9% magnesium, 46.8% phosphate, 37.4% calcium, and 1.2% liver function tests. Twenty-six patients (4.0%) had a change in management owing to postoperative laboratory test results. Of these 26 women, 88% experienced a change in clinical status that would have otherwise prompted testing. Only 3 (0.5% of entire cohort) were asymptomatic: 1 received a blood transfusion for asymptomatic anemia, and the other 2, who did not carry a diagnosis of diabetes mellitus, had interventions for hyperglycemia. On univariable analysis, peripheral and cerebrovascular disease, diabetes mellitus with end-organ damage, and a Charlson Comorbidity Index of ≥3 were associated with increased odds of change in management; these were not significant on multivariable analysis. Routine postoperative laboratory evaluation in this cohort increased hospital costs by $292,000.
Routine postoperative laboratory tests are unlikely to lead to significant changes in management for women undergoing minimally invasive hysterectomy for endometrial cancer, and may increase cost without providing a discernible clinical benefit. In the setting of strict postoperative guidelines, laboratory tests should be ordered when clinically indicated rather than as part of routine postoperative management for women undergoing minimally invasive hysterectomy for endometrial cancer.
A pathologic chemotherapy response score (CRS) is used to grade ovarian cancer response to neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of the CRS in a single institution ...cohort.
A retrospective review of all consecutive epithelial ovarian cancer patients undergoing interval debulking surgery (IDS) after NACT from 2016 to 2017 were included. Clinical, pathologic, surgical, outcomes, and genetic data were abstracted from medical records. CRS was assigned by pathology based on a section of omentum as follows: 1 = minimal response, 2 = moderate response, and 3 = near complete response.
Among the 50 subjects, 14 (28%) were classified as CRS1, 29 (58%) as CRS2, and 7 (14%) as CRS3. The majority of patients were diagnosed with high grade serous histology (94%). Most women in this cohort underwent either an optimal or complete cytoreduction to no gross residual disease (96%). Women in the CRS2 group were most likely to have a pathogenic variant (51.7%) while those in the CRS1 were least likely (7.1%). Most women recurred regardless of CRS. CRS was not associated with progression-free survival (log-rank p = 0.82) or overall survival (log-rank p = 0.30).
Though previous data support the use of CRS as a prognostic indicator, we failed to show a correlation between CRS and survival in our continuous single institution cohort. The high rate of optimal debulking across all CRS groups in this study may mitigate the prognostic significance of the scoring system. Nevertheless, tumors that respond poorly to traditional chemotherapy should remain of avid interest for potential novel therapies.
•Chemotherapy response score at time of surgery after NACT for ovarian cancer is not prognostic of survival.•High rates of optimal debulking were achieved regardless of CRS.•Development of novel therapies for tumors that respond poorly to chemotherapy remains of high importance.
•HPV vaccination is not consistently offered (31.3%) to patients being treated for high-grade cervical or vulvar dysplasia.•Patients undergoing surgery for HPV-related dysplasia are likely to accept ...HPV vaccination (65.6%).•The rate at which adjuvant HPV vaccination is offered may improve over time.
Eligibility for the human papillomavirus (HPV) vaccine now includes adults 27 through 45 years. It has not been reported how providers are addressing HPV vaccination in patients with existing preinvasive disease. Our objectives were to determine the rates at which vaccination is offered to and received by patients undergoing surgery for high-grade cervical or vulvar dysplasia.
This was a single-institution retrospective cohort study including patients ages 18 through 45 years undergoing surgery for high-grade cervical or vulvar dysplasia from 10/2018 to 2/2020. Our primary outcome was the rate at which HPV vaccination was discussed at the pre- and/or post-operative visits. The secondary outcome was the rate of vaccine uptake in these individuals. Characteristics of those offered HPV vaccination were compared to those not offered vaccination.
Of the 115 patients included, 36 (31.3%) had HPV vaccination addressed in the perioperative setting. Thirty-two of these patients had never been vaccinated, and 21 of these (65.6%) went on to receive partial or complete HPV vaccination. Those in whom HPV vaccination was addressed were more likely to be under 27 years (RR 3.2; 95% CI 2.1–4.8) and less likely to be smokers (RR 0.5; 95% CI 0.2–0.9) or have prior excisional procedures (RR 0.3; 95% CI 0.1–0.9). The absolute rate of discussing HPV vaccination with patients improved from 26.0% within six months of vaccine age eligibility expansion, to 35.4% after six months (P = 0.32).
Providers did not consistently address HPV vaccination among patients being treated for high-grade cervical or vulvar dysplasia despite the potential benefits. However, a high proportion of these patients are amenable to vaccination. Quality improvement initiatives are warranted to increase the rate of HPV vaccine counseling in this context.
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