Relationship between frailty and nutrition: Refining predictors of mortality after primary cytoreductive surgery for ovarian cancer.

OBJECTIVE: We aimed to examine the interplay between frailty and nutritional status on 90-day mortality after primary cytoreductive surgery (PCS) for ovarian cancer (OC). METHODS: Patients with OC who underwent PCS from 1/2/2006-4/30/2018 at a single institution were identified. Frailty index (FI) includes 30 items and is calculated summing across all the item scores and dividing by the total; frailty was defined as FI ≥0.15. Nutritional status was considered impaired when preoperative serum albumin was <3.5 g/dL. Logistic regression was used to analyze the association between FI (continuous) and albumin status (binary) and 90-day postoperative mortality. RESULTS: A total of 533 patients (mean age, 64.4 years) were included, the majority were stage IIIC disease and serous histology. Albumin was <3.5 g/dL in 87 patients (16.3%) and 113 patients (21.2%) were considered frail. Median FI was 0.07 (IQR 0.03, 0.13). Postoperative 90-day mortality occurred in 24 patients (4.5%). Mortality within 90 days was higher amongst patients with low albumin (12/87, 13.8%), regardless of frailty status (13.8% [9/65] non-frail and 13.6% [3/22] frail patients). Ninety-day mortality in patients with normal albumin (n = 446) was over twice as likely in frail versus non-frail patients (5.5% [5/91] vs. 2.0% [7/355], respectively, p = 0.08). A model to assess 90-day mortality that included both FI and low albumin significantly improved the overall discrimination compared to low albumin alone (AUC 0.76 vs. 0.68 p = 0.03). CONCLUSION: Our findings suggest that frailty and nutrition are both related to 90-day mortality. Preoperative interventions to improve functional and nutritional characteristics are needed.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial.

BACKGROUND: After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. OBJECTIVE: This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. STUDY DESIGN: Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. RESULTS: Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). CONCLUSION: This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Measuring the impact of specific surgical complications after ovarian cancer cytoreductive surgery on short-term outcomes.

OBJECTIVE: We sought to measure the impact of specific peri-operative complications after primary cytoreductive surgery on relevant patient outcomes and use of resources. METHODS: A cohort of patients with advanced ovarian cancer who underwent primary cytoreductive surgery at two institutions (2006-2016) were studied. Specific known complications ('exposures') within 30 days of surgery were evaluated to determine the impact on outcomes. Exposures included bowel leak, superficial surgical site infection, deep surgical site infection, venous thromboembolic event, and cardiac event. Outcomes were prolonged lengths of stay, readmission or non-home discharge, reoperation, organ failure, delay to adjuvant chemotherapy, and 90-day mortality. Population attributable risk (PAR) was used to estimate the proportion of adverse outcomes that could be prevented by elimination of a causal exposure and considers both the strength of the association and the prevalence of the complication; adjusted PARs (aPAR) were calculated using adjusted relative risks (aRR) adjusted for stage (IIIC vs IV) and American Society of Anesthesiology score (<3 vs ≥3). RESULTS: A cohort of 892 patients was included. Each of the evaluated exposures had an impact on readmission/non-home discharge (aPAR range 5.3 to 13.5). A venous thromboembolic event was significantly associated with 90-day mortality (aRR=2.9 (95% CI 1.3 to 6.7); aPAR=8.6 (95% CI -1.8 to 19.1)) and organ failure (aRR=4.7 (95% CI 2.3 to 9.5); aPAR=13.9 (95% CI 2.8 to 25.1)). Similarly, a cardiac event was most strongly associated with organ failure and was very impactful (aPAR=19.0 (95% CI 6.8 to 31.1)).Bowel leak was a major contributor to poor outcome, including reoperation (aPAR=45.5 (95% CI 34.3 to 56.6)), organ failure (aPAR=13.6 (95% CI 2.6 to 24.6)), readmission/non-home discharge (aPAR=5.3 (95% CI 1.6 to 9.0)), delay to adjuvant chemotherapy (aPAR=5.9 (95% CI 2.3 to 9.4)), and prolonged lengths of stay (aPAR=13.0 (95% CI 9.1 to 16.9)). CONCLUSION: Going beyond reporting complications using common scales to measure their genuine impact provides important information for providers, patients, and payers. We report that less frequent exposures, including a venous thromboembolic event, cardiac events, and bowel leaks, have a high impact on patients and use of resources.

Endometrial cancer with positive sentinel lymph nodes: pathologic characteristics of metastases as predictors of extent of lymphatic dissemination and prognosis.

OBJECTIVES: To assess predictors of extensive lymph node dissemination and non-vaginal recurrence in patients with endometrial cancer with positive sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer who underwent primary surgery with SLN mapping and had at least one positive node between October 2013 and May 2019 were included. Positive SLNs were reviewed, and cases were classified according to the location of the metastasis (extracapsular vs intracapsular), and the size of the largest SLN metastasis (isolated tumor cells, micrometastasis, macrometastasis). Associations were assessed based on fitting logistic regression models and Cox proportional hazards models. RESULTS: A total of 103 patients met the inclusion criteria: including 36 (34.9%) with isolated tumor cells, 27 (26.2%) with micrometastasis, and 40 (38.8%) with macrometastasis. Notably, 71.4% of patients exhibiting extracapsular SLN metastases had multiple positive SLNs (p=0.008). Extracapsular invasion (adjusted odds ratio (aOR) 5.81, 95% CI 1.4 to 23.6) and age (aOR=1.8, 95% CI 1.1 to 3.0) emerged as independent predictors of multiple positive SLNs. Among the 38 patients who underwent a backup pelvic lymphadenectomy, 18 (47.4%) presented with positive pelvic non-SLNs, a phenomenon more prevalent in patients with macrometastasis (p=0.004).Independent predictors of non-vaginal recurrence included SLN macrometastasis (adjusted hazard ratio (aHR) 3.3, 95% CI 1.3 to 8.3), non-endometrioid histology (aHR=3.7, 95% CI 1.5 to 9.3), and cervical stromal invasion (aHR=5.5, 95% CI 2.0 to 14.9). Among the 34 patients with isolated tumor cells and endometrioid histology, 3 (9%) experienced a recurrence, all of whom had not received any adjuvant chemotherapy or external beam radiotherapy. CONCLUSION: Patients with positive SLN macrometastasis are independently associated with extensive lymphatic dissemination and distant recurrences. The risk of multiple positive SLNs increases with the extracapsular location of the SLN metastasis and with age. Independent uterine pathologic predictors of non-vaginal recurrence are non-endometrioid histology and cervical stromal invasion.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer.

OBJECTIVES: The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer. METHODS: A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. RESULTS: Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3-7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1-2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99). CONCLUSION: The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

Incidence of sentinel lymph node metastases in apparent early-stage endometrial cancer: a multicenter observational study.

OBJECTIVE: Ultrastaging is accurate in detecting nodal metastases, but increases costs and may not be necessary in certain low-risk subgroups. In this study we examined the risk of nodal involvement detected by sentinel lymph node (SLN) biopsy in a large population of apparent early-stage endometrial cancer and stratified by histopathologic characteristics. Furthermore, we aimed to identify a subgroup in which ultrastaging may be omitted. METHODS: We retrospectively included patients who underwent SLN (with bilateral mapping and no empty nodal packets on final pathology) ± systematic lymphadenectomy for apparent early-stage endometrial cancer at two referral cancer centers. Lymph node status was determined by SLN only, regardless of non-SLN findings. The incidence of macrometastasis, micrometastasis, and isolated tumor cells (ITC) was measured in the overall population and after stratification by histotype (endometrioid vs serous), myometrial invasion (none, <50%, ≥50%), and grade (G1, G2, G3). RESULTS: Bilateral SLN mapping was accomplished in 1570 patients: 1359 endometrioid and 211 non-endometrioid, of which 117 were serous. The incidence of macrometastasis, micrometastasis, and ITC was 3.8%, 3.4%, and 4.8%, respectively. In patients with endometrioid histology (n=1359) there were 2.9% macrometastases, 3.2% micrometastases, and 5.3% ITC. No macro/micrometastases and only one ITC were found in a subset of 274 patients with low-grade (G1-G2) endometrioid endometrial cancer without myometrial invasion (all <1%). The incidence of micro/macrometastasis was higher, 2.8%, in 708 patients with low-grade endometrioid endometrial cancer invading <50% of the myometrium. In patients with serous histology (n=117), the incidence of macrometastases, micrometastasis, and ITC was 11.1%, 6.0%, and 1.7%, respectively. For serous carcinoma without myometrial invasion (n=36), two patients had micrometastases for an incidence of 5.6%. CONCLUSIONS: Ultrastaging may be safely omitted in patients with low-grade endometrioid endometrial cancer without myometrial invasion. No other subgroups with a risk of nodal metastasis of less than 1% have been identified.

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

OBJECTIVES: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment. METHODS: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC. RESULTS: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC. CONCLUSION: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT.

Validation of a risk-based algorithm to reduce poor operative outcomes after complex surgery for ovarian cancer.

OBJECTIVE: We developed an algorithm that identifies patients at high risk of morbidity/mortality after cytoreductive surgery for advanced ovarian cancer. We have previously shown that the Mayo triage algorithm reduces operative mortality internally, followed by validation using an external low complexity national dataset. However, validation in a higher complexity surgical setting is required before widespread acceptance of this approach, and this was the goal of our study. METHODS: We included patients who underwent debulking surgery (including primary or interval debulking surgery) for stage IIIC/IV ovarian cancer between October 2011 and November 2019 (SCORPION trial patients until May 2016 and non-trial patients thereafter) at Fondazione Policlinico A Gemelli, Italy. Using the algorithm, we classified patients as either high-risk or triage-appropriate and compared 30-day grade 3+ complications and 90-day mortality using a χ2 test or Fisher's exact test. RESULTS: A total of 625 patients were included. The mean age was 58.7±11.4 years, 73.6% (n=460) were stage IIIC, and 63.0% (n=394) underwent primary debulking surgery. Surgical complexity was intermediate or high in 82.6% (n=516) of patients (95.7% (n=377) for primary surgery and 60.2% (n=139) for interval surgery), and 20.3% (n=127) were classified as high-risk. When compared with triage-appropriate patients, high-risk patients had (1) a threefold higher rate of 90-day mortality (6.3% vs 2.0%, p=0.02); (2) a higher likelihood of 90-day mortality following a grade 3+ complication (25.9% vs 10.0%, p=0.05); and (3) comparable rates of grade 3+ complications (21.3% vs 16.1%, p=0.17). CONCLUSION: The evidence-based triage algorithm identifies patients at high risk of morbidity/mortality after cytoreductive surgery. Triage high-risk patients are poor candidates for surgery when complex surgery is required. This algorithm has been validated in heterogeneous settings (internal, national, and international) and degree of surgical complexity. Risk-based decision making should be standard of care when planning surgery for patients with advanced ovarian cancer, whether primary or interval surgery.

Comparison of the Contracted Accordion, Expanded Accordion, and Clavien-Dindo complication grading scales after ovarian cancer cytoreduction.

OBJECTIVE: To compare the ability of current complication reporting scales (Contracted Accordion Scale, Expanded Accordion Scale, Clavien-Dindo Scale) to reflect the severity of patient outcomes after cytoreductive surgery for ovarian cancer. METHODS: We included all patients undergoing primary debulking surgery for stage IIIC/IV ovarian cancer from 2006 to 2016 at two expert centers for ovarian cancer. Complications within 30 days of surgery were graded according to three scales. Outcomes included length of stay, mortality (90-day), and delayed initiation of chemotherapy (>42 days after surgery). Correlations were assessed using the Spearman rank correlation, and comparisons between groups were evaluated using the Wilcoxon rank-sum test and the χ2 test. RESULTS: Among the 892 patients, 185 (20.7%) patients had a grade 3 or higher complication per all scales. Patients with grade 3 or higher complications (compared with those with none, grade 1 or grade 2) had longer length of stay, higher 90-day mortality, and delayed initiation of chemotherapy. The expanded scales (Expanded Accordion Scale and Clavien Dindo Scale) provided a more refined characterization of outcome compared with the Contracted Accordion Scale. However, mortality was actually found to be as high as 25.0% for grade 5 complications using the Expanded Accordion Scale. Patients with organ failure or requiring an invasive procedure had significantly worse outcomes than those without either complication, highlighting the importance of separating these events. CONCLUSIONS: All three scales demonstrated general correlation with important outcomes after ovarian cancer surgery. However, the expanded scales (Clavien Dindo Scale and Expanded Accordion Scale) used important events commonly encountered after cytoreductive surgery, provided a more refined view of the severity of complications, and should be used in reporting outcomes in ovarian cancer.

Impact of comorbidities and extent of lymphadenectomy on quality of life in endometrial cancer patients treated with minimally invasive surgery in the era of sentinel lymph nodes.

OBJECTIVE: To identify predictors of quality of life (QoL) among patients who undergo surgical staging with sentinel lymph node (SLN) biopsy or lymphadenectomy for endometrial cancer. METHODS: Patients who underwent minimally invasive surgery for primary endometrial cancer at the Mayo Clinic from October 2013 to June 2016 were mailed a 30-item QoL in Cancer survey (QLQ-C30) and a validated 13-item lower extremity lymphedema screening questionnaire. Patients who answered <50% of the items or had a pre-operative history of lymphedema were excluded. Multivariable linear regression models were fit to evaluate predictors of QoL using inverse-probability of treatment weighting to adjust for differences at the time of the surgery between the lymphadenectomy and SLN groups. RESULTS: The 221 patients included in the analysis were stratified into two groups: patients who underwent (1) bilateral lymphadenectomy as 'backup' after SLN mapping (lymphadenectomy group; n=101) or (2) SLN removal with or without side-specific lymphadenectomy (SLN group; n=120). On multivariable analysis, obesity, lower extremity lymphedema, and kidney disease had significant (p<0.05) and clinically meaningful negative impacts on global QoL. Declines in average adjusted global QoL scores were marked (19.7 points lower) in patients with BMI ≥40 kg/m2 and lower extremity lymphedema compared with non-obese patients without lower extremity lymphedema. In contrast, there was only a 2.9 point difference in the adjusted average global QoL score between the SLN and lymphadenectomy groups. CONCLUSIONS: Lower extremity lymphedema coupled with obesity predicts poorer QoL in patients who undergo surgical staging for endometrial cancer. In this population, reduction of lower extremity lymphedema by performing SLN instead of lymphadenectomy and earlier targeted interventions may improve patients' QoL. Future research focusing on targeted interventions is needed.

Prognostic factors in patients with endometrial cancer with isolated lymphatic recurrence.

OBJECTIVE: To analyze the clinicopathological features and outcomes in patients with endometrial cancer with isolated lymphatic recurrence after lymphadenectomy, stratified by different isolated lymphatic recurrence sites and treatment approaches. METHODS: We retrospectively reviewed all surgically treated patients with endometrial cancer, identifying those with recurrence. We defined primary isolated lymphatic recurrence as the first and unique evidence of recurrence in lymph node-bearing areas, without concomitant vaginal, hematogenous, or peritoneal recurrence. Isolated lymphatic recurrences were classified as pelvic, para-aortic, distant, or multiple sites. Our primary outcome was cause-specific survival after diagnosis of the recurrence. RESULTS: Among 4216 patients with surgically staged endometrial cancer, we identified 66 (1.6%) women with isolated lymphatic recurrence. The overall median cause-specific survival for patients with isolated lymphatic recurrence was 24 months. Although cause-specific survival was not significantly different between the four isolated lymphatic recurrence groups (p=0.21), 7 of 15 (47%) patients with isolated lymphatic recurrence in the para-aortic area were long-term survivors. At multivariate Cox regression, the absence of lymphovascular space invasion and grade 1 histology in the primary tumor were significantly associated with improved cause-specific survival. In addition, patients with isolated lymphatic recurrence who underwent surgery for recurrence (with/without other associated therapies) had improved cause-specific survival compared with patients who did not undergo surgery, also after adjusting for age. CONCLUSIONS: Low-grade histology and absence of lymphovascular space invasion in the primary tumor were predictors of improved prognosis in patients with endometrial cancer with isolated lymphatic recurrence. In addition, in this retrospective cohort, patients with isolated lymphatic recurrence who were selected for eradicative surgical treatment had improved cause-specific survival.

Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer.

OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

Contemporary Use of Hormonal Therapy in Endometrial Cancer: a Literature Review.

OPINION STATEMENT: Most endometrial cancers are estrogen receptor and progesterone receptor positive. Hormonal therapy in endometrial cancer is best used in patients with low-grade disease and hormone receptor positivity. Though not standard of care, hormonal treatment can be considered in endometrial cancer treatment in both the early-stage upfront setting for patients who are not surgical candidates and in advanced and recurrent endometrial cancer. In patients who desire fertility preservation or who are not surgical candidates, levonorgestrel intrauterine device and oral progesterone are preferred treatment options. In patients with advanced and metastatic disease, there is no standard-of-care second-line treatment, and hormonal treatment is a widely accepted option for low-grade disease. Beyond progesterone, selective estrogen receptor modulators, aromatase inhibitors, gonadotropin-releasing hormone agonists, and fulvestrant are hormonal treatment options. New therapies, such as MTOR inhibitors and CDK 4/6 inhibitors, have been extensively studied in breast cancer and are shown to be useful in conjunction with hormonal therapies particularly when there is suspected resistance to anti-estrogen treatment. Hormonal therapies also tend to be better tolerated than chemotherapy agents, making them a desirable option particularly in patients with lower performance status. Results from ongoing clinical trials will hopefully help shed light on the use of combination treatment in patients with hormone receptor-positive, low-grade metastatic, and recurrent endometrial cancer.

Overall survival after surgical staging by lymph node dissection versus sentinel lymph node biopsy in endometrial cancer: a national cancer database study.

OBJECTIVE: Substituting lymphadenectomy with sentinel lymph node biopsy for staging purposes in endometrial cancer has raised concerns about incomplete nodal resection and detrimental oncological outcomes. Therefore, this study aimed to investigate the association between the type of lymph node assessment and overall survival in endometrial cancer accounting for node status and histology. METHODS: Women with stage I-III endometrial cancer who underwent hysterectomy and lymph node assessment from January 2012 to December 2015 were identified in the National Cancer Database. Patients who underwent neoadjuvant therapy, had previous cancer, and whose follow-up was less than 90 days were excluded. Multivariable Cox proportional hazards regression analyses were performed to assess factors associated with overall survival. RESULTS: Of 68 614 patients, 64 796 (94.4%) underwent lymphadenectomy, 1777 (2.6%) underwent sentinel node biopsy only, and 2041 (3.0%) underwent both procedures. On multivariable analysis, neither sentinel lymph node biopsy alone nor sentinel node biopsy followed by lymphadenectomy was associated with significantly different overall survival compared with lymphadenectomy alone (HR 0.92, 95% CI 0.73 to 1.17, and HR 0.91, 95% CI 0.77 to 1.08, respectively). When stratified by lymph node status, sentinel node biopsy alone or followed by lymphadenectomy was not associated with different overall survival, both in patients with negative (HR 0.95, 95% CI 0.73 to 1.24, and HR 1.04, 95% CI 0.85 to 1.27, respectively) or positive (HR 0.91, 95% CI 0.54 to 1.52, and HR 0.77, 95% CI 0.57 to 1.04, respectively) lymph nodes. These findings held true when sentinel node biopsy alone and sentinel node biopsy plus lymphadenectomy groups were merged, and on stratification by histotype (type one vs type 2) or inclusion of only complete lymphadenectomy (at least 10 pelvic nodes and at least one para-aortic node removed). In all analyses, age, Charlson-Deyo score, black race, AJCC pathological T stage, grade, lymphovascular invasion, brachytherapy, and adjuvant chemotherapy were independently associated with overall survival. DISCUSSION: No difference in overall survival was found in patients with endometrial cancer who underwent sentinel node biopsy alone, sentinel node biopsy followed by lymphadenectomy, or lymphadenectomy alone. This observation remained regardless of node status, histotype, and lymphadenectomy extent.

Excision of Deep Endometriosis of the Rectosigmoid: Individualizing Care to the Presenting Pathology.

STUDY OBJECTIVE: To highlight different surgical approaches for managing deep infiltrating endometriosis involving the rectosigmoid colon. DESIGN: Demonstration of specific surgical techniques with educational narrated video footage. SETTING: Bowel endometriosis is reported in 3.8% to 37% of patients with endometriosis [1]. Most commonly, the rectosigmoid colon is involved. Pelvic ultrasound and magnetic resonance imaging may be useful in diagnosis and for surgical planning [2]. Treatment options include observation, medications, or surgery. There are various surgical techniques that can be used for excision of deep infiltrating endometriosis involving the rectosigmoid colon. Serosal shaving, discoid resection, and complete resection are the possible types of surgical interventions that are demonstrated in this surgical education video at an academic medical center. Serosal shaving is used for lesions with minimal involvement of the muscularis. It can be done sharply or with electrosurgery and it is imperative to assess bowel integrity after shaving. Discoid resection is used for lesions with muscularis involvement, <3 cm in size, and encompassing less than one-third to a half of the bowel circumference. Full-thickness discoid bowel resection can be done in various ways including manual resection with primary suture closure, regular stapler transabdominally, or EEA stapler (Medtronic EEA Circular Stapler, Minneapolis, MN) transrectally. Segmental resection is used for lesions >3 cm in size, involving >50% of the bowel circumference, or for multifocal lesions. Various suture and stapler methods exist for this technique. INTERVENTIONS: Based on the imaging and intraoperative findings, a surgical technique was chosen and demonstrated. The types of surgical techniques demonstrated include laparoscopic serosal shaving, discoid resection with manual resection and primary suture closure, discoid resection with EEA stapler, and segmental resection. CONCLUSION: Knowledge of different surgical approaches to excise endometriosis is essential to appropriately address a patient's unique pathology. The choice of which surgical technique to use should include consideration of the location of the lesion, depth and circumference of involvement, and the number of nodules present.

Surgical Science-Simbionix Robotic Hysterectomy Simulator: Validating a New Tool.

STUDY OBJECTIVE: To gather validity evidence for and determine acceptability of Surgical Science-Simbionix Hysterectomy Modules for the DaVinci Xi console simulation system (software; 3D Systems by Simbionix [now Surgical Science-Simbionix], Littleton, CO, and hardware; Intuitive Surgical, Inc., Sunnyvale, CA) and evaluate performance benchmarks between novice and experienced or expert surgeons. DESIGN: Prospective education study (Messick validity framework). SETTING: Multicenter, academic medical institutions. PARTICIPANTS: Residents, fellows, and faculty in obstetrics and gynecology were invited to participate at 3 institutions. Participants were categorized by experience level: fewer than 10 hysterectomies (novice), 10 to 50 hysterectomies (experienced), and more than 50 hysterectomies (expert). A total of 10 novice, 10 experienced, and 14 expert surgeons were included. INTERVENTIONS: Participants completed 4 simulator modules (ureter identification, bladder flap development, colpotomy, complete hysterectomy) and a qualitative survey. Simulator recordings were reviewed in duplicate by educators in minimally invasive gynecologic surgery using the Modified Global Evaluative Assessment of Robotic Skills (GEARS) rating scale. MEASUREMENTS AND MAIN RESULTS: Most participants felt that the simulator realistically simulated robotic hysterectomy (64.7%) and that feedback provided by the simulator was as or more helpful than feedback from previous simulators (88.2%) but less helpful than feedback provided in the operating room (73.5%). Participants felt that this simulator would be helpful for teaching junior residents. Simulator-generated metrics correlated with GEARS performance for the bladder flap and ureter identification modules in multiple domains including total movements and total time for completion. GEARS performance for the bladder flap module correlated with experience level (novice vs experienced/expert) in the domains of interest and total score but did not consistently correlate for the other procedural modules. Performance benchmarks were evaluated for the bladder flap module for each GEARS domain and total score. CONCLUSION: The modules were well received by participants of all experience levels. Individual simulation modules appear to better discriminate between novice and experienced/expert users than overall simulator performance. Based on these data and participant feedback, the use of individual modules in early residency education may be helpful for providing feedback and may ultimately serve as 1 component of determining readiness to perform robotic hysterectomy.

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

Appropriate triage allows aggressive primary debulking surgery with rates of morbidity and mortality comparable to interval surgery after chemotherapy.

OBJECTIVE: Morbidity and mortality (M/M) after primary debulking surgery (PDS) is often cited as a rationale for neoadjuvant chemotherapy and interval debulking surgery (IDS). We tested if using an evidence-based algorithm to identify patients fit for surgery would reduce M/M after PDS to that seen after IDS. METHODS: We included women who underwent PDS or IDS for advanced epithelial ovarian cancer (EOC) (1/2012-7/2016) guided by the use of a prospective triage algorithm. Outcomes were compared after applying inverse-probability of treatment weighting (IPTW) to adjust for covariate imbalance. RESULTS: Of 334 included patients, 232 (69.5%) underwent PDS and 102 (30.5%) were triaged to IDS. Relative to IDS group, PDS patients were younger (63.9 vs 67.5 years, P=0.01), were less likely to have low albumin (16.8% vs. 32.4%, P<0.001), had longer median operative times (315 vs 263 min, P <0.001), more high complexity surgeries and fewer low complexity surgeries (27.2% vs. 11.8% and 18.5% vs 36.3% respectively, P<0.001). The rates of the following outcomes were comparable for PDS and IDS, respectively: successful cytoreduction (complete, 62.5% vs 66.7%, P=0.47 and optimal, 95.3% vs 98.0%, P=0.36), 30-day grade 3+ complications (IPTW-adjusted 18.3% vs. 12.9%, P=0.22), 90-day mortality (IPTW-adjusted, 2.2% vs. 3.8%, P=0.42), length of hospitalization (P=0.29), and postoperative chemotherapy delivery (P=0.83). 3-year overall survival was higher for PDS group (IPTW-adjusted 64.1% vs. 42.6%, P=0.001). CONCLUSIONS: Use of our validated triage strategy allowed us to offer 70% of women with advanced EOC PDS surgery. Despite more complex surgery, M/M after this approach is low and comparable to IDS, with similar rates of complete resection and superior OS. Use of a validated triage system should be utilized when considering PDS vs neoadjuvant chemotherapy.

Image-guided tumor ablation in gynecologic oncology: Review of interventional oncology techniques and case examples highlighting a collaborative, multidisciplinary program.

As interventional oncology services within radiology mature, image-guided ablation techniques are increasingly applied to recurrent gynecologic malignancies. Ablation may be performed using thermal techniques like cryoablation, microwave ablation, or radiofrequency ablation, as well as non-thermal ones, such as focused ultrasound or irreversible electroporation. Feasibility and approach depend on tumor type, size, number, anatomic location, proximity of critical structures, and goals of therapy. Current indications include local control of limited metastatic disease or palliation of painful bone metastases refractory or unsuitable to conventional therapies. Technical aspects of these procedures, including methods to protect nearby critical structures are presented through illustrative examples. Cases amenable to image-guided ablation include, but are not limited to, hepatic or pulmonary metastases, musculoskeletal metastases, retroperitoneal nodal metastases, pelvic side wall disease, abdominal wall disease, and vaginal or vulvar tumors. Protective maneuvers, such as hydro-displacement of bowel, neuromonitoring, and retrograde pyeloperfusion through ureteral stents, permit safe ablation despite close proximity to vulnerable nerves or organs. Image-guided ablation offers an alternative modality to achieve local tumor control without the risks associated with surgery or systemic treatment in appropriately selected patients. A multidisciplinary approach to use of image-guided ablation includes collaboration between gynecologic oncology, interventional radiology, anesthesia, urology and radiation oncology teams allowing for appropriate patient-centered case selection. Long-term follow up and additional studies are needed to determine the oncologic benefits of such techniques.