Limor Helpman

Revisiting the paradigm: Asymptomatic high-grade endometrial cancer diagnosis is not associated with improved outcomes

To compare the survival of women with high grade endometrial cancer between asymptomatic and women presenting bleeding symptoms. An Israel Gynecologic Oncology Group multi-center retrospective cohort study. The study included women who underwent surgery for high-grade endometrial cancer. We compared outcomes between women presenting with postmenopausal bleeding and asymptomatic women diagnosed with high-grade endometrial cancer. Recurrence-free, disease-specific and overall survival were assessed using the Kaplan Meier method and compared using the log-rank test. Risk factors for recurrence and death were evaluated using Cox regression analysis; the primary exposure variable assessed was the presence of postmenopausal bleeding. Of the 584 women with high-grade histology, 498 (85.3 %) presented with postmenopausal bleeding and 86 (14.7 %) were asymptomatic. The median follow-up was 52 months (12-120 months). There was no difference in recurrence-free survival between women diagnosed with postmenopausal bleeding and asymptomatic women (70.1 % vs.64.6 % at 5 years, p = 0.35, respectively). There were no significant differences in disease-specific survival (66.3 % vs. 64.2 % at 5 years, p = 0.83) or in overall survival (56.4 % vs. 58 % at five years, p = 0.55) between study groups. The multivariate Cox regression analysis did not reveal any significant association between postmenopausal bleeding and survival. In this study, the diagnosis of high-grade endometrial cancer in asymptomatic women was not associated with earlier disease stage at diagnosis. In women with incidental ultrasonographic findings of a thickened endometrium or polyp, routine invasive evaluation may be unnecessary.

Variability in endometrial carcinoma pathology practice: opportunities for improvement with molecular classification

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5-95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1-41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study

Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×10 Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×10 Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

Increased ultrasonographic endometrial thickness is associated with poor survival in patients with endometrial cancer: An Israel gynecologic oncology group study

We aimed to assess the association of pre-operatively evaluated ultrasonographic endometrial thickness with outcomes of patients with endometrial cancer. An Israel Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer who underwent surgery between 2002 and 2014 in one of eleven academic centers. Patients were categorized by endometrial thickness into two groups: ≤20 mm and >20 mm. Clinical and pathological features were compared using Student T-test for continuous variables and Chi-square or Fisher's exact test for categorical variables. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. 1113 patients in whom endometrial thickness data was recorded were the subject of this study and included 2 groups: ≤20 mm (n = 930), >20 mm (n = 183). The median follow-up was 52 months (range 12-120 months). Patients with endometrial thickness >20 mm had significantly lower recurrence-free survival (log rank, p 20 mm remained independently associated with an increased hazard of recurrence and death (HR = 1.77, 95% CI 1.07-2.96, p = .03 for recurrence; and HR = 1.68; 95% CI 1.07-2.65; p = .03 for overall survival). In patients with endometrial cancer, endometrial thickness>20 mm as measured preoperatively by ultrasound, is independently associated with decreased recurrence-free and overall survival. This finding suggests that thick endometrium may be considered as one of the risk factors for poor prognosis.

Inguinofemoral sentinel lymph node biopsy by scar injection in vulvar cancer: an assessment of feasibility and long-term outcomes

Performing inguinofemoral sentinel lymph node biopsy for vulvar cancer following a previous vulvar excision, often referred to as 'scar injection', is debated. To assess the feasibility of sentinel lymph node biopsy following scar injection and the long-term outcomes in patients undergoing this procedure. We conducted a retrospective observational cohort study of patients with vulvar cancer. We assessed detection rates and outcomes in patients who underwent sentinel lymph node biopsy by scar injection and compared them with patients who had injection around a visible tumor and with patients who had an inguinofemoral lymphadenectomy following previous vulvar excision. Sentinel node detection rates are described per patient and per groin and are compared using Χ Data were analyzed for 173 groins in 97 patients. At least one sentinel lymph node was detected in 162 (94%) groins examined, and detection rate did not differ whether the groin was assessed following tumor injection (n=122, 94%) or scar injection (n=40, 93%; p=0.85). Patients in the scar-injection group had less frequent lymph node metastases (p<0.02), smaller tumors (p<0.001), and more superficial invasion (p<0.02). Median follow-up was 34.7 months (range 0-108). Scar injection was not independently associated with recurrence or death on multivariable analysis, and depth of invasion was the only independent predictor of disease recurrence (hazards ratio (HR)=1.14, p=0.03). Recurrence and survival were also comparable for patients who had a sentinel lymph node biopsy or inguinofemoral lymphadenectomy following previous vulvar excision (log rank p=0.30; p=0.67). Sentinel lymph node biopsy by scar injection is feasible and demonstrates similar long-term outcomes in patients having scar or tumor injections, and in patients following previous tumor excision undergoing sentinel lymph node biopsy or lymphadenectomy.

Evaluating equity of access and predictors of minimally invasive hysterectomy for endometrial and cervical cancer from 2000 to 2017 in Ontario, Canada: A population‐based cohort study

AbstractIntroductionWe sought to assess the uptake of minimally invasive hysterectomy among patients with endometrial and cervical cancer in Ontario, Canada, and assess the equity of access to minimally invasive surgery (MIS) by evaluating associations with patient, disease, institutional, and provider factors.MethodsThis is a retrospective population‐based cohort study of hysterectomy for endometrial and cervical cancer in Ontario (2000–2017). Surgical approach, clinicopathologic, sociodemographic, institutional, and provider factors were identified through administrative databases. Fisher's exact, χ2, Wilcoxon rank sum, logistic regression, and Cox proportional hazards modeling were used to explore factors associated with MIS.ResultsA total of 27 652 patients were included. In total, 6199/24 264 (26%) endometrial and 842/3388 (25%) cervical cancer patients received MIS. The proportion of MIS to open surgeries increased from &lt;0.1% in 2000 to over 55% in 2017 (odds ratio [OR] = 1.31, confidence interval [CI] = 1.28–1.34). Low‐income quintile, rurality, low hospital volume, nonacademic hospital, nongynecologic oncology surgeon, and earlier year of surgeon graduation were associated with reduced odds of MIS (OR &lt; 1).ConclusionsThe uptake of MIS hysterectomy increased steadily over the time period. Receipt of MIS is dependent upon multiple social determinants, provider variables, and systems factors. These disparities raise concern for health equity in Ontario and have significant implications for health systems planning and resource allocation.

Safety of vaginal surgery for early-stage cervical cancer: A retrospective multicenter cohort study.

Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.