Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab.

OBJECTIVES: To determine the clinical predictors of response rate, progression-free survival (PFS), and overall survival (OS) to pembrolizumab in advanced or recurrent, mismatch repair deficient (MMRd) or Microsatellite Instability-High (MSI-H) endometrial adenocarcinomas. METHODS: A retrospective, single institution study was conducted among women with recurrent or advanced MMRd or MSI-H endometrial adenocarcinomas treated with single-agent pembrolizumab at our institution from 2017 to 2021. Logistic regression was used for univariable and multivariable analyses. PFS and OS were estimated using the methods of Kaplan and Meier and modeled via Cox proportional hazards regression. Log-rank test was used for intergroup comparisons based on body mass index (BMI). RESULTS: Among the 44 patients included in the analysis, the median BMI was 32.9 (range 18.5-51.8). Median cycles of pembrolizumab given was 11.5 (range 2-37). Median follow-up was 33 months (range 5-61) with a response rate of 63.6% and stable disease rate of 75%. When stratified by obesity status (BMI≥30), disease control rate was 59.8% in patients with a BMI < 30 and 85.2% in patients with a BMI≥30 patients (p = 0.05). On multivariable analysis, obesity was associated with increased rate of disease control (OR 4.03, 95%CI 1.09, 28) while prior smoking was associated with decreased rate of disease control (OR 0.18, 95%CI 0.03, 0.85). PFS was significantly increased among patients with a BMI≥30 (p = 0.03) but OS was similar (p = 0.5). CONCLUSION: In this retrospective study, obesity is associated with increased rates of disease control and improved PFS in patients treated with pembrolizumab for recurrent or advanced MMRd/MSI-H endometrial adenocarcinomas.

Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors.

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions. OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. STUDY DESIGN: This is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumors of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least 1 documented recurrence, and treatment/treatment planning at the MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery, and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier, and were modeled via Cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. RESULTS: Among the 369 patients with adult granulosa cell tumors of the ovary in the registry, 149 patients met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (hazard ratio, 0.37; 95% confidence interval, 0.17-0.81, P=.01) and multivariable analyses (hazard ratio, 0.42; 95% confidence interval, 0.19-0.92; P=.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared with those who did not undergo cytoreductive surgery (181.92 vs 61.56 months, respectively; P=.002). Overall survival benefit remained statistically significant on multivariable analysis (hazard ratio, 0.28; 95% confidence interval, 0.11-0.67; P=.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (hazard ratio, 0.43; 95% confidence interval, 0.26-0.70; P=.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (hazard ratio, 0.74; 95% confidence interval, 0.42-1.26; P=.27). CONCLUSION: Among those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may have a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumors of the ovary.

Clinical outcomes of leuprolide acetate in the treatment of recurrent ovarian granulosa cell tumors.

BACKGROUND: The optimal treatment of recurrent ovarian granulosa cell tumors is not known. Preclinical studies and small case series have suggested direct antitumor activity of gonadotropin-releasing hormone agonists in the treatment of this disease, but little is known about the efficacy and safety of this approach. OBJECTIVE: This study aimed to describe patterns of use and clinical outcomes of leuprolide acetate in a cohort of patients with recurrent granulosa cell tumors. STUDY DESIGN: This was a retrospective cohort study of patients enrolled in the Rare Gynecologic Malignancy Registry at a large cancer referral center and affiliated county hospital. Patients meeting inclusion criteria had a diagnosis of recurrent granulosa cell tumor and received either leuprolide acetate or traditional chemotherapy as cancer treatment. Outcomes were separately examined for leuprolide acetate used as adjuvant treatment, maintenance therapy, and the treatment of gross disease. Demographic and clinical data were summarized using descriptive statistics. Progression-free survival was calculated from the initiation of treatment to the date of disease progression or death, and compared between groups with the log-rank test. The 6-month clinical benefit rate was defined as the percentage of patients without disease progression 6 months after starting therapy. RESULTS: Sixty-two patients received a total of 78 leuprolide acetate-containing therapy courses, owing to 16 instances of retreatment. Of these 78 courses, 57 (73%) were for treatment of gross disease, 10 (13%) were adjuvant to tumor reductive surgery, and 11 (14%) were for maintenance therapy. Patients had received a median of 2 (interquartile range, 1-3) systemic therapy regimens before their first leuprolide acetate treatment. Tumor reductive surgery (100% [62/62]) and platinum-based chemotherapy (81% [50/62]) were common before first leuprolide acetate exposure. The median duration of leuprolide acetate therapy was 9.6 months (interquartile range, 4.8-16.5). Nearly half of the therapy courses were single-agent leuprolide acetate (49% [38/78]). Combination regimens most often included an aromatase inhibitor (23% [18/78]). Disease progression was the most common cause of discontinuation (77% [60/78]); only 1 patient (1%) discontinued leuprolide acetate because of adverse events. In the treatment of gross disease, the 6-month clinical benefit rate for first use of leuprolide acetate was 66% (95% confidence interval, 54-82). Median progression-free survival was not statistically different compared with that which followed chemotherapy (10.3 months [95% confidence interval, 8.0-16.0] vs 8.0 months [95% confidence interval, 5.0-15.3]; P=.3). CONCLUSION: In a large cohort of patients with recurrent granulosa cell tumors, the 6-month clinical benefit rate of first-time leuprolide acetate treatment of gross disease was 66% and progression-free survival was comparable to patients treated with chemotherapy. Leuprolide acetate regimens were heterogeneous, but significant toxicity was rare. These results support leuprolide acetate as safe and effective for the treatment of relapsed adult granulosa cell tumors in the second line and beyond.

Lymphatic Mapping and Sentinel Node Biopsy in High-Grade Uterine Cancers.

PURPOSE OF REVIEW: Sentinel lymph node (SLN) mapping has been adopted as an acceptable method of lymph node evaluation in the surgical staging for low-grade endometrial cancer. In this review, we analyze the literature on the utility of SLN mapping in high-grade endometrial cancer. RECENT FINDINGS: SLN mapping in high-grade endometrial cancer demonstrates similar high detection rates and diagnostic accuracy as seen in low-grade endometrial cancers. However, obtaining sufficient operator experience (at least 30 cases) and following SLN mapping algorithm continues to be essential to preserving diagnostic accuracy. Although limited in retrospective study design and short-term follow-up, current studies have not demonstrated inferior survival outcomes of SLN mapping compared to traditional lymphadenectomy. SLN mapping is an acceptable and accurate method of lymph node evaluation in high-grade endometrial cancer. Future prospective studies are needed to evaluate long-term oncologic outcomes between SLN mapping and systematic lymphadenectomy in this patient population.

The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial.

Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibitors in GCT patients. Here, we present a case series of GCT patients treated with pembrolizumab who were enrolled in a phase II basket trial in advanced, rare solid tumors (ClinicalTrials.gov: NCT02721732). Cases We identified 5 patients with recurrent GCT (4 adult and 1 juvenile type); they had an extensive history of systemic therapy at study enrollment (range, 3-10), with most regimens resulting in less than 12 months of disease control. Pembrolizumab was administered in these patients, as per trial protocol. Although there were no objective responses according to the irRECIST guidelines, 2 patients with adult-type GCT experienced disease control for ≥ 12 months (565 and 453 days). In one, pembrolizumab represented the longest duration of disease control compared to prior lines of systemic therapy (565 days vs. 13 months). In the other, pembrolizumab was the second longest systemic therapy associated with disease control (453 days vs. 22 months) compared to prior lines of therapy. In this patient, pembrolizumab was discontinued following withdrawal of consent. PD-L1 expression was not observed in any baseline tumor samples. Pembrolizumab was well tolerated, with no grade 3 or 4 treatment-related adverse events. Conclusions Although our results do not support the routine use of pembrolizumab monotherapy in unselected GCT patients, some patients with adult-type GCT may derive a clinical benefit, with a low risk of toxicity. Future studies should investigate the role of immunotherapy and predictors of clinical benefit in this patient population.

Toxicity and efficacy of the combination of pembrolizumab with recommended or reduced starting doses of lenvatinib for treatment of recurrent endometrial cancer.

OBJECTIVE: We reviewed our institutional data to evaluate toxicity and efficacy outcomes of pembrolizumab/lenvatinib in recurrent endometrial cancer in a "real-world" clinical setting and to compare the impact of reduced lenvatinib starting dose on outcomes. METHODS: Retrospectively, we reviewed toxicity, treatment responses, and survival outcomes of patients with recurrent endometrial cancer who received ≥1 cycle of pembrolizumab/lenvatinib. We compared subgroups based on lenvatinib starting dose (recommended [20 mg] vs reduced [<20 mg]) and histologic type. RESULTS: We analyzed 70 patients (recommended dose cohort, n = 16; reduced dose cohort, n = 54). The most common starting dose was 14 mg daily. Compared to the reduced dose cohort, the recommended dose cohort had a significantly higher mean number of lenvatinib dose reductions due to side effects (1.1 vs. 0.4; p = 0.003) and significantly shorter median time to treatment toxicity (1.3 vs. 3.7 days; p = 0.0001). Response rates did not differ significantly between the recommended and reduced dose cohorts (28.6% vs. 38.3%, respectively; p = 0.752). Two patients, both in the reduced dose cohort, had complete responses. Patients with carcinosarcoma histology had response and clinical benefit rates of 25% (3 of 12) and 58.3% (7 of 12), respectively. There were no differences between the 2 dose cohorts with respect to progression-free (p = 0.245) or overall survival (p = 0.858). CONCLUSION: In clinical practice, a lower starting dose of lenvatinib (14 mg daily) in combination with pembrolizumab was safe and efficacious in recurrent endometrial cancer. The combination produced responses in endometrial carcinosarcomas. Larger studies are required to validate these findings.

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics.

OBJECTIVE: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). DATA SOURCES: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. METHODS: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4-43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I2=0%). CONCLUSION: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Immuno-Oncology for Gynecologic Malignancies.

Patients with advanced and/or recurrent gynecologic cancers derive limited benefit from currently available cytotoxic and targeted therapies. Successes of immunotherapy in other difficult-to-treat malignancies such as metastatic melanoma and advanced lung cancer have led to intense interest in clinical testing of these treatments in patients with gynecologic cancers. Currently, in the realm of gynecologic oncology, the FDA-approved use of immune checkpoint inhibitors is limited to microsatellite instability-high cancers, cancers with high tumor mutational burden, and PD-L1-positive cervical cancer. However, there has been an exponential growth of clinical trials testing immunotherapy approaches both alone and in combination with chemotherapy and/or targeted agents in patients with gynecologic cancers. This chapter will review some of the major reported and ongoing immunotherapy clinical trials in patients with endometrial, cervical, and epithelial ovarian cancer.

The added value of sentinel node mapping in endometrial cancer.

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.

Immuno-oncology for Gynecologic Malignancies.

Patients with advanced and/or recurrent gynecologic cancers derive limited benefit from currently available cytotoxic and targeted therapies. Successes of immunotherapy in other difficult-to-treat malignancies such as metastatic melanoma and advanced lung cancer have led to intense interest in clinical testing of these treatments in patients with gynecologic cancers. Currently, in the realm of gynecologic oncology, the FDA-approved use of immune checkpoint inhibitors is limited to microsatellite instable cancers and PD-L1-positive cervical cancer. However, there has been an exponential growth of clinical trials testing immunotherapy approaches, both alone and in combination with chemotherapy and/or targeted agents, in patients with gynecologic cancers. This chapter reviews some of the major reported and ongoing immunotherapy clinical trials in patients with endometrial, cervical, and epithelial ovarian cancer.

Risk factors for lymph nodes involvement in obese women with endometrial carcinomas.

OBJECTIVE: To assess risk factors for lymph node involvement in patients with endometrial cancer and a body-mass index (BMI) ≥30 kg/m2. MATERIALS AND METHODS: A retrospective analysis was performed of obese patients diagnosed with endometrial carcinoma between 2007 and 2015, treated in a single center in Montreal. Preoperative variables evaluated were age, BMI, parity, and preoperative ASA score, grade, CA-125 and histology. Odds ratios (OR) and hazard ratios (HR) and their respective 95% confidence intervals (95%CI) were calculated using multivariable logistic regression and Cox proportional hazard models. RESULTS: The study included 230 women with BMI ≥30, 223 (97.0%) had complete staging. Pelvic lymph node involvement was detected in 26 patients (11.3%). Sentinel node detection and pelvic lymph node dissection decreased with increasing BMI (adjusted OR 0.86, 95%CI 0.76-0.97 and 0.76, 95%CI 0.59-0.96, respectively, per 1 kg/m2 increment). Pelvic lymph node involvement was inversely correlated with BMI (adjusted OR 0.88, 95%CI 0.79-0.99) and present in 16/85 (18.8%), 6/56 (10.7%), and 4/82 (4.9%) of patients with a BMI of 30.0-34.9, 35.0-39.9, and ≥40.0 kg/m2, respectively. Preoperative CA-125 was associated with lymph node involvement (adjusted OR 2.77, 95%CI 1.62-4.73, per quartile increment). CONCLUSION: Pelvic lymph node dissection might be omitted in selected cases of morbidly obese patients with failed sentinel nodes mapping and a low CA-125.

Triple tracer (blue dye, indocyanine green, and Tc99) compared to double tracer (indocyanine green and Tc99) for sentinel lymph node detection in endometrial cancer: a prospective study with random assignment.

OBJECTIVE: Sentinel lymph node (SLN) mapping is increasingly being used in the treatment of apparent early-stage endometrial cancer. The aim of this study was to evaluate whether three tracers (blue dye, indocyanine green (ICG), and technetium-99 (Tc99)) performed better than two (ICG and Tc99). STUDY DESIGN: Prospective study of all consecutive patients (n=163) diagnosed with clinical early-stage endometrial cancer from 2015 to 2017. All patients were randomly assigned to receive a mixture of ICG and Tc99 with or without blue dye. Subgroup analysis for detection rates was performed for each group (double versus triple tracer). RESULTS: One hundred and fifty-seven patients met the inclusion criteria. Eighty patients received ICG and Tc99 with unilateral and bilateral SLN detection rates of 97.5% and 81.3%, respectively. Seventy-seven patients received all three tracers with unilateral and bilateral detection rates of 93.5% and 80.5%, respectively. Only one patient in the triple tracer group was detected by blue dye alone. No significant differences were noticed in unilateral or bilateral detection rates between the two groups, nor in the detection of lymph node metastasis. CONCLUSION: The addition of blue dye to ICG and Tc99 did not demonstrate any improvement in SLN detection.

Incorporating robotic surgery into the management of ovarian cancer after neoadjuvant chemotherapy.

INTRODUCTION: With the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III-IV ovarian cancer. METHODS: All patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III-IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III-IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery. RESULTS: A total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24-88), 78% had stage III disease, and the median follow-up time was 37 months (5.6-91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10-1250 mL), and the median hospital stay was 1 day. CONCLUSION: Robotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.

Influence of Resident Involvement in Obstetrics and Gynaecology Surgery on Surgical Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVE: The effect of resident involvement during obstetrics and gynaecology (OB/GYN) surgery on surgical outcomes is unclear. This study sought to review the evidence systematically for the influence of resident participation in OB/GYN surgery on (1) operative time, (2) estimated blood loss, and (3) perioperative complications. METHOD: Published studies were identified via searches of PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov databases. The study included randomized or observational studies that compared outcomes for OB/GYN surgery performed by attending surgeons alone or with residents. Risk ratios or mean differences were extracted from the studies. A random effect model was performed for each outcome, with subgroup analysis by type of surgery and study quality. RESULTS: A total of 13 studies were included in the meta-analysis, comprising 40 968 patients in seven countries. Surgical procedures performed only by attending surgeons had shorter operative times (mean difference 18.20 minutes; 95% CI 13.58-22.82), whereas surgical procedures with resident involvement were associated with an increased risk of blood transfusion (risk ratio 1.23; 95% CI 1.08-1.41). There were no observable differences in risk of estimated blood loss, wound infection, urologic injury, viscus injury, or return to the operating room. Significant heterogeneity (I2 >50%) was present in one of seven outcomes. CONCLUSION: Resident participation in OB/GYN surgery is associated with longer operative times and increased risk of blood transfusion; however, other perioperative complications are not increased.

Unexpected locations of sentinel lymph nodes in endometrial cancer.

INTRODUCTION: To evaluate the anatomical location of sentinel lymph nodes (SLN) following intra-operative cervical injection in endometrial cancer. METHODS: All consecutive patients with endometrial cancer undergoing sentinel lymph node mapping were included in this prospective study following intra-operative cervical injection of tracers. Areas of SLN detection distribution were mapped. RESULTS: Among 436 patients undergoing SLN mapping, there were 1095 SLNs removed, and 7.9% of these SLNs found in 13.1% of patients, were detected in areas not routinely harvested during a standard lymph node dissection. These included the internal iliac vein, parametrial, and pre-sacral areas. The SLN was the only positive node in 46.1% (15/36) of cases with successful mapping and completion lymphadenectomy, including 3 cases where the sentinel node in the atypical location was the only node with metastatic disease. CONCLUSION: SLN mapping using intra-operative cervical injection is capable to map out areas not typically included in a standard lymphadenectomy. The sentinel node is the most relevant lymph node to analyze and may enable to discover metastatic disease in unusual areas.

Impact of sentinel lymph node mapping on recurrence patterns in endometrial cancer.

BACKGROUND: Sentinel lymph node (SLN) mapping has emerged as a promising solution to the ongoing debate regarding lymphadenectomy in the initial surgical management of endometrial cancer. Currently, little is known about its possible impact on location of disease recurrence compared to systematic lymphadenectomy. METHODS: In this retrospective study, 472 consecutive patients with endometrial cancer who underwent either SLN mapping (SLN cohort, n=275) or systematic lymphadenectomy (LND cohort, n=197) from sequential, non-overlapping historical time points were compared. Clinical characteristics were extracted from a prospectively gathered electronic database. Both overall and pelvic sidewall recurrence free survival (RFS) were evaluated at 48-month post-operative follow-up. RESULTS: No significant difference in overall RFS could be identified between the cohorts at 48months (HR 0.74, 95% CI 0.43-1.28, p=0.29). However, the SLN cohort had improved pelvic sidewall RFS compared to the LND cohort (HR 0.32, 95% CI 0.14-0.74, p=0.007). The pelvic sidewall recurrences accounted for 30% of recurrences in the SLN cohort (8 out of 26 recurrences) compared to 71.4% in the LND cohort (20 out of 28 recurrences). CONCLUSIONS: SLN mapping may enable more efficient detection of the LNs at greatest risk of metastasis and help to guide adjuvant therapy, which in turn seems to decrease the risk of pelvic sidewall recurrences.

Outcome of robotic surgery for endometrial cancer as a function of patient age.

OBJECTIVE: This study aimed to evaluate and compare robot-assisted surgical staging on clinical outcomes, including quality of life and survival, as a function of patient age. METHODS: Evaluation and comparison of perioperative morbidity, survival, and postoperative quality of life after prospective accumulation of clinical information including outcome measures for patients with endometrial cancer during the first 5 years of a robotic program, based on the following 3 age categories: women older than 80 years, women between 70 and 80 years, and women younger than 70 years. RESULTS: All consecutive patients with endometrial cancer undergoing robotic surgery (n = 303) were included, with 197 women younger than 70 years, 75 women between 70 and 80 years, and 31 women older than 80 years. There were significantly more patients with advanced stage (stage II to IV in 17%, 34%, and 35%, P = 0.02) and grade 3 disease (26%, 43%, and 58%, P = 0.002) with increasing age. The perioperative data showed similar grade I or II complications (Clavien-Dindo classification) between the groups, but significantly more grade III and IV complications for women older than 80 years compared with women 80 years or younger (10% vs 1%, P = 0.004). The time needed to resume chore activities was significantly shorter for patients 70 years or older than patients younger than 70 years [8.9 (8.7) vs 18.8 (25.5) days, P = 0.048]. Overall, all patients irrespective of age were highly satisfied with the procedure. There was no difference between young and elderly patients for disease-free survival (P = 0.99). CONCLUSIONS: Patient's age did not influence minor postoperative morbidity or overall satisfaction after robotic assisted surgery for endometrial cancer. Elderly patients had more major postoperative morbidity but resumed activities quicker than younger patients.

The impact of qualitative research on gynaecologic oncology guidelines.

OBJECTIVE: Inherent in the care provided to patients with cancer is an important psychosocial element which has been explored scientifically through qualitative research. The purpose of our study was to evaluate the availability of qualitative research in gynaecologic oncology and to measure its integration in gynaecologic oncology practice guidelines. METHODS: We searched Medline, CINHAL, Scopus, and Web of Science databases to identify the availability of qualitative research conducted in the past 20 years on the three most prevalent gynaecologic cancers: endometrial, ovarian, and cervical cancer. National and international practice guidelines on management of gynaecologic cancers were selected using the National Guideline Clearinghouse website, the Society of Obstetricians and Gynaecologists of Canada website, and the Standards and Guidelines Evidence directory of cancer guidelines. Bibliometric analysis was used to determine the frequency of qualitative references cited in these guidelines. RESULTS: One hundred thirteen qualitative research papers on gynaecologic cancers were identified focusing on psychological impacts, social dynamics, and doctor-patient interactions during cancer treatment and recovery. Among the 15 national and international clinical practice guidelines identified on management of gynaecologic cancer, there were a total of 2272 references, and of these only three references citing qualitative research were identified (0.1%) in only one of the 15 practice guidelines. CONCLUSION: Although qualitative research is being carried out in gynaecologic oncology, its integration into clinical practice guidelines is essentially absent. Efforts to narrow the gap between qualitative research and clinical practice are essential in ensuring a comprehensive approach to the treatment of patients with gynaecologic cancer.

Objectif : Les soins offerts aux patientes atteintes d'un cancer comptent une importante composante psychosociale, laquelle a été explorée de façon scientifique par l'intermédiaire de la recherche qualitative. Notre étude avait pour objectif d'évaluer la disponibilité de la recherche qualitative en gynéco-oncologie et d'en mesurer l'intégration aux directives cliniques relevant du domaine de la gynéco-oncologie. Méthodes : Nous avons mené des recherches dans diverses bases de données (Medline, CINHAL, Scopus et Web of Science) en vue de cerner la disponibilité de la recherche qualitative menée au cours des 20 dernières années au sujet des trois cancers gynécologiques les plus prévalents : les cancers de l'endomètre, de l'ovaire et du col utérin. Des directives cliniques nationales et internationales portant sur la prise en charge des cancers gynécologiques ont été sélectionnées au moyen du site Web National Guideline Clearinghouse, du site Web de la Société des obstétriciens et gynécologues du Canada, et du répertoire Standards and Guidelines Evidence de lignes directrices sur le cancer. Une analyse bibliométrique a été utilisée pour déterminer la fréquence des références qualitatives citées dans les directives cliniques en question. Résultats : Nous avons identifié 113 mémoires de recherche qualitative portant sur des cancers gynécologiques qui se centraient sur les effets psychologiques, sur la dynamique sociale et sur les interactions médecin-patiente dans le cadre du traitement anticancéreux et de la récupération. Au sein des 15 directives cliniques nationales et internationales portant sur la prise en charge des cancers gynécologiques que nous avons identifiées, nous avons dénombré un total de 2 272 références; parmi ces dernières, seules trois références citant une recherche qualitative ont été identifiées (0,1 %), et ce, au sein d'une seule directive clinique parmi les 15 qui ont été analysées. Conclusion : Bien que des efforts de recherche qualitative soient menés dans le domaine de la gynéco-oncologie, l'intégration de leurs résultats aux directives cliniques est essentiellement inexistante. La mise en œuvre de mesures visant à combler l'écart entre la recherche qualitative et la pratique clinique s'avère essentielle pour assurer l'utilisation d'une approche exhaustive envers le traitement des patientes qui présentent un cancer gynécologique.

Impact of robotics on the outcome of elderly patients with endometrial cancer.

OBJECTIVE: To evaluate the impact of introducing a robotics program on clinical outcome of elderly patients with endometrial cancer. METHODS: Evaluation and comparison of peri-operative morbidity and disease-free interval in 163 consecutive elderly patients (≥70years) with endometrial cancer undergoing staging procedure with traditional open surgery compared to robotic surgery. RESULTS: All consecutive patients ≥70years of age with endometrial cancer who underwent robotic surgery (n=113) were compared with all consecutive patients ≥70years of age (n=50) before the introduction of a robotic program in December 2007. Baseline patient characteristics were similar in both eras. Patients undergoing robotic surgery had longer mean operating times (244 compared with 217minutes, p=0.009) but fewer minor adverse events (17% compared with 60%, p<0.001). The robotics cohort had less estimated mean blood loss (75 vs 334mL, p<0.0001) and shorter mean hospital stay (3 vs 6days, p<0.0001). There was no difference in disease-free survival (p=0.61) during the mean follow-up time of 2years. CONCLUSION: Transitioning from open surgery to a robotics program for the treatment of endometrial cancer in the elderly has significant benefits, including lower minor complication rate, less operative blood loss and shorter hospitalization without compromising 2-year disease-free survival.

Prospective quality of life outcomes following robotic surgery in gynecologic oncology.

PURPOSE: To characterize the health-related quality of life (HRQL) of patients undergoing robotic surgery for the treatment of gynecologic cancers. METHODS: 211 patients completed a quality of life questionnaire before surgery. Postoperative questionnaires, consisting of the same assessment with the addition of postoperative questions, were given at 1 week, 3 weeks, 3, 6, and 12 months after surgery. The Functional Assessment of Cancer Therapy-General (FACT-G) and its subscales were used to evaluate HRQL. Patient-rated body image was evaluated using the Body Image Scale. Statistical significance was measured by the Wilcoxon signed-rank test. Minimally important difference (MID) values were analyzed to evaluate clinical significance. RESULTS: Overall HRQL and body image decreased at 1 week after surgery and returned to baseline by 3 weeks. Physical and functional well-being decreased at 1 week after surgery and returned to baseline by 3 months after surgery. However, using MID criteria, physical well-being returned to baseline by 3 weeks. Social well-being did not change significantly. Emotional well-being increased immediately by 1 week after surgery. CONCLUSION: Patient reported HRQL outcomes following robotic surgery for the treatment of gynecologic cancers suggests a rapid return to pre-surgery values.