Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Racial disparities in non-recommendation of adjuvant chemotherapy in stage II-III ovarian cancer.

OBJECTIVES: To identify patient factors associated with not receiving a recommendation for adjuvant chemotherapy after primary surgery for ovarian cancer. METHODS: This retrospective cohort study used the National Cancer Database (NCDB) data from 2004 to 2015 to identify patients with stage II-III ovarian cancer who underwent primary surgery. Multivariate logistic regression analyses evaluated factors associated with notation in the NCDB that "chemotherapy was not recommended/administered because it was contraindicated due to patient risk factors (i.e., comorbid conditions, advanced age)." Survival data were assessed via Kaplan-Meier analyses. RESULTS: Of the 48,245 patients who met the inclusion criteria, 522 (1.08%) did not receive adjuvant chemotherapy because it was determined to be contraindicated. In multivariate analyses, independent predictors for not receiving a recommendation for adjuvant chemotherapy were age ≥ 70 years old (adjusted odds ratio, aOR = 2.43, p < 0.0001), non-zero Charlson-Deyo comorbidity scores (score 1, aOR = 1.41, p = 0.002; score ≥ 2, aOR = 2.57, p < 0.0001), and Black race (aOR = 2.12, p < 0.0001). For Black patients, recommendation against adjuvant chemotherapy occurred at a younger median age (64.5 years vs. 72 years) and was associated with lower 5-year survival (25.9% vs. 40.3%, p < 0.0001). CONCLUSIONS: Patients with ovarian cancer who underwent surgery but did not receive chemotherapy "because it was contraindicated due to patient risk factors" were older and had higher comorbidity scores. Even after controlling for these differences, Black patients were disproportionately not recommended for chemotherapy, which was associated with worse survival. Determining eligibility for adjuvant chemotherapy requires an individualized approach, and the possible influence of racial bias on risk estimation should be further investigated.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

Incidence of Gynecologic Cancers in Women after Uterine Artery Embolization.

STUDY OBJECTIVE: To characterize the short-term incidence of gynecologic cancer after undergoing uterine artery embolization (UAE). DESIGN: Retrospective cohort study. SETTING: Commercial insurance claims database. PATIENTS: Total of 15 393 United States women aged 18 to 64 years who underwent UAE between 2007 and 2017. INTERVENTIONS: We used the IBM MarketScan (Armonk, NY) claims to identify adult women without previous gynecologic cancer diagnoses undergoing UAE between 2007 and 2017. Database queries identified women with any diagnostic or procedure codes related to gynecologic malignancies occurring in the first 3 years after UAE. A malignancy diagnosis was suggested by recurrent malignancy-related claims not linked exclusively to diagnostic testing (e.g., transvaginal ultrasound) and malignancy codes linked to tissue pathology claims. Incidence of malignancy diagnosis was calculated. Rates of endometrial sampling in the year before UAE were identified. MEASUREMENTS AND MAIN RESULTS: Thirty-one women undergoing UAE had gynecologic cancer diagnoses within 3 years of the procedure (22 of 31, 71% uterine cancers; 7 of 31, 23% ovarian cancers; and 2 of 31, 6% cervical cancers). On average, cancer diagnoses were made 1.1 ± 0.9 years after UAE. One in 497 women undergoing UAE was diagnosed with a gynecologic malignancy within 3 years, with an incidence of 1.1 malignancies per 1000 person-years. Cancer incidence increased with age at the time of UAE: short-term malignancy diagnoses were made in 1 in 377 women aged 45 to 54 years, and 1 in 79 women aged 55 to 64 years. In the year before UAE, 28% (4311 of 15 362) of women without cancer, and 23% (5 of 22) of women diagnosed with uterine cancer had preprocedural endometrial sampling. CONCLUSION: These data can inform risk/benefit counseling and shared decision-making regarding UAE and its alternatives. Short-term malignancies after UAE highlight the importance of preprocedure evaluation in symptomatic women and women with age-related risk.

Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma.

OBJECTIVE: Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) for a subset of women with advanced ovarian cancer. It remains unresolved whether NACT-IDS increases the risk of platinum resistance. We compared response to chemotherapy in patients that received NACT-IDS vs. PDS. METHODS: From our Cancer Registry database we identified patients with stages IIIC and IV epithelial ovarian cancer who underwent treatment from January, 2005 to December, 2010. Standard univariate analyses were performed, as were multivariable analysis with logistic regression. The Kaplan-Meier method was used to generate survival data. RESULTS: The study population consisted of 425 patients, 95 (22.3%) underwent NACT-IDS and 330 (77.6%) PDS. After the initial platinum-based chemotherapy, 42 (44.2%) women in the NACT-IDS group were considered to have platinum resistant disease, compared to 103 (31.2%) in the PDS group (P=0.01). When multivariate logistic regression was used to control for factors independently associated with platinum resistance, NACT-IDS was no longer associated with an initial increased risk. However, in women that had a recurrence and were retreated with platinum-based chemotherapy, 32 (88.8%) in the NACT-IDS group had developed a recurrence within six months and were considered platinum resistant, compared to 62 (55.3%) in the PDS (P<0.001). CONCLUSION: In women with EOC that have a recurrence and are treated again with platinum-based chemotherapy, NACT-IDS appears to increase the risk of platinum resistance.

Preoperative leukocytosis imposes an increased risk of recurrence and death among patients with nonendometrioid endometrial carcinoma.

OBJECTIVE: To evaluate the impact of preoperative leukocytosis among patients with nonendometrioid endometrial carcinoma. METHODS: The medical records of all patients with nonendometrioid endometrial carcinoma who underwent surgical treatment between January 2005 and December 2010 were retrospectively reviewed. The patients were separated into 2 groups based on the presence or absence of preoperative leukocytosis (white blood cell count ≥ 10,000/µL). The groups were then compared with respect to pathologic findings, progression-free survival, and overall survival. RESULTS: A total of 222 patients were identified, and preoperative leukocytosis was observed in 33 patients (14.9%). The leukocytosis group was associated with a larger mean size of the primary tumor (6.8 vs 4.6 cm, P = 0.016) and a greater percentage of patients with cervical stromal involvement (36.4% vs 20.1%, P = 0.039), adnexal involvement (42.4% vs. 22.8%, P = 0.017), and pelvic/para-aortic lymph node involvement (50% vs 27.4%, P = 0.025). On multivariate analysis, preoperative leukocytosis was independently associated with an increased risk of recurrence (hazard ratio, 2.07; 95% confidence interval, 1.12-3.84) and an increased risk of death (hazard ratio, 3.33; 95% confidence interval, 2.01-5.53). CONCLUSIONS: Among patients with nonendometrioid endometrial carcinoma, preoperative leukocytosis is independently associated with an increased risk of recurrence and death.

The significance of preoperative leukocytosis in endometrial carcinoma.

OBJECTIVE: To evaluate the impact of preoperative leukocytosis among patients with endometrial carcinoma. METHODS: The medical records of all patients that underwent surgical treatment for endometrial carcinoma between January 2005 and December 2010 were retrospectively reviewed. Patients were separated into two groups based on the presence or absence of preoperative leukocytosis (WBC ≥ 10,000 cells per µl). The groups were then compared with respect to pathologic findings, progression-free survival and overall survival. RESULTS: 1144 patients were identified, 156 (13.6%) with preoperative leukocytosis and 988 (86.4%) without leukocytosis. The leukocytosis group had a greater percentage of patients with stage 3 (15.4% vs. 9.8%, crude p=0.02) and 4 (7.1% vs. 3.0%, crude p=0.007) disease. Leukocytosis was associated with a greater mean tumor size (4.4 vs. 3.4 cm, p=0.0002) and a greater percentage of patients with cervical stromal involvement (14.8% vs. 8.7%, crude p=0.02), adnexal involvement (14.1% vs. 7.5%, crude p=0.007) and lymphvascular space invasion (24% vs. 16.3%, crude p=0.02). On multivariate analysis, mean tumor size (OR, 95% CI; 1.10, 1.02-1.18) remained significantly associated with preoperative leukocytosis. There was no difference between groups, with respect to time to recurrence. However, leukocytosis was independently associated with an increased risk of death (HR, 95% CI; 1.69, 1.07-2.68). CONCLUSIONS: Preoperative leukocytosis, among endometrial cancer patients, was independently associated with increasing tumor size and independently imposed an increased risk of death.

A case of vaginal adenosis with gastric differentiation.

•Vaginal adenosis is a non-obligate pre-cursor for vaginal clear cell carcinoma.•Vaginal adenosis is rare and presents with a variety of signs and symptoms.•Unclear link between adenosis and carcinoma without diethylstilbestrol exposure.•Surveillance with physical examinations, imaging and biopsies is recommended.

Inflammatory and Nutritional Serum Markers as Predictors of Peri-operative Morbidity and Survival in Ovarian Cancer.

AIM: To identify preoperative nutritional and inflammatory markers that predict perioperative outcomes in patients with ovarian cancer (OC). PATIENTS AND METHODS: Fifty patients who underwent primary debulking for advanced (stage III/IV) OC were selected from a cohort of patients who underwent surgery between 2002 and 2009. We analyzed C-reactive protein (CRP), interleukin-6 (IL6) and albumin and their impact on mortality and surgical outcomes. RESULTS: Two patients were excluded since they did not have adequate measurements of CRP and IL6. Among the remaining patients, 25 (52%) were ≥70 years old. Nine (19%), 12 (25%) and 12 (25%) patients had low serum albumin (<3.0 g/dl), elevated CRP (≥70 mg/l) and elevated IL6 (≥24 pg/ml), respectively. Age was a significant predictor of non-home discharge (p=0.01). Low serum albumin (<3.0 g/dl) was a predictor of death within 6 month (p=0.03). Elevated CRP (≥70 mg/l) was a predictor of non-home discharge (p=0.02), death within 6 months (p=0.02), death within 12 months (p=0.04), and longer hospital stay (p=0.01). Elevated IL6 (≥24 pg/ml) was a predictor of non-home discharge (p=0.002) and surgical complications (p=0.02), and also associated with longer hospital stay (p=0.03). CONCLUSION: Poor nutrition and high inflammatory status negatively influence surgical and oncological outcomes of patients with OC. These preoperative markers can be used for selection of patients for neoadjuvant chemotherapy at high risk of short survival, non-home discharge and long hospital stay.