Cost-effectiveness of lenvatinib plus pembrolizumab versus chemotherapy for recurrent mismatch repair-proficient endometrial cancer after platinum-based therapy.

OBJECTIVE: The recent Study 309-KEYNOTE-775 showed improved survival for lenvatinib plus pembrolizumab compared to chemotherapy in patients with recurrent endometrial cancer. We created a decision model to compare the cost-effectiveness of lenvatinib plus pembrolizumab in patients with recurrent mismatch repair-proficient (pMMR) endometrial cancer who had progressed after first-line chemotherapy. METHODS: A Markov model was created to simulate the clinical trajectory of 10,000 patients with recurrent pMMR endometrial cancer. The initial decision point in the model was treatment with ether lenvatinib plus pembrolizumab or chemotherapy (doxorubicin or dose-dense paclitaxel). Model probabilities, utility values and costs were derived with assumptions drawn from published literature. A cycle length of 3 months and a time horizon of 2 years was used. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2020 US dollars/QALYs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Chemotherapy was the least costly strategy at $66,693 followed by lenvatinib plus pembrolizumab ($193,590). Lenvatinib plus pembrolizumab resulted in more patients being alive at 2 years (lenvatinib plus pembrolizumab: 367, chemotherapy: 109). Chemotherapy was cost-effective compared with lenvatinib plus pembrolizumab (ICER: $164,493/QALYs). Lenvatinib plus pembrolizumab became cost-effective when its cost was reduced by $1553 per month (7.8% reduction). CONCLUSION: For patients with recurrent pMMR endometrial cancer Lenvatinib plus pembrolizumab is associated with greater survival but is more costly than chemotherapy. The cost of lenvatinib and pembrolizumab would have to be reduced by approximately 7% to be considered cost-effective.

Estrogen replacement therapy and non-hormonal medication use among patients with uterine cancer.

OBJECTIVE: As the prognosis for endometrial cancer is excellent, management of the effects of estrogen deprivation has an important influence on quality of life. We examined the trends in the use of estrogen replacement therapy (ERT) and non-hormonal medications among patients with uterine cancer following surgery. METHODS: The MarketScan Database was used to identify patients 18-49 years who underwent hysterectomy plus oophorectomy and those aged 50-75 years who underwent hysterectomy between 2008 and 2020. ERT and non-hormonal treatments of menopause were identified preoperatively and postoperatively. After propensity score balancing, difference-in-differences (DID) analyses were performed to compare the pre-and-postoperative changes in ERT and non-hormonal medication use between groups. The trends in postoperative use of ERT were assessed and tested using Cochran-Armitage trend tests. RESULTS: A total of 19,700 patients with uterine cancer and 185,150 controls were identified. Overall, postoperative ERT use decreased for both age groups and for patients with and without uterine cancer. The DID in ERT use between those with uterine cancer and those with benign pathology after hysterectomy was -37.1% (95% CI, -40.5 to -33.6%) for patients 18-49 years of age and - 10.4% (95% CI, -10.9 to -9.9%) for those 50-75 years. The DID for non-hormonal medication use between those with uterine cancer and those with benign pathology after hysterectomy was 11.2% (95% CI, 7.8 to 14.7%) for younger patients and 3.4% (95% CI, 2.9 to 4.0%) for those 50-75 years. The postoperative new ERT use has been declining over time in patients with uterine cancer in those 18-49 years of age (P = .02) and those 50-75 years of age (P < .001). CONCLUSIONS: The use of ERT is uncommon and has declined over time in patients with uterine cancer. Conversely, non-hormonal medications are more commonly used among patients with uterine cancer.

Hospital Volume and Quality of Care for Emergency Gynecologic Care.

OBJECTIVE: To evaluate the association between hospital volume and the quality of gynecologic emergency care for tubal ectopic pregnancies, ovarian torsion, and pelvic inflammatory disease (PID). METHODS: In this cross-sectional analysis, we analyzed patients who presented for emergency care for tubal ectopic pregnancies, ovarian torsion, and PID using the Premier Healthcare Database from 2006 to 2020. We measured the following outcomes: methotrexate use for ectopic pregnancy, ovarian cystectomy for torsion, and guideline-based antibiotic use for PID. For each condition, we measured outlier hospitals that performed the above interventions at below the 10th percentile. Multivariable logistic regression models were used to analyze associations between outlier care and hospital factors such as annualized mean case volume, urban or rural location, teaching status, bed capacity, and geographic region, as well as hospital-level patient population factors, including age, insurance status, and race. RESULTS: A total of 602 hospitals treated patients with tubal ectopic pregnancies, of which 21.9% were outliers, with no cases managed with methotrexate. Of 512 hospitals treating patients with ovarian torsion, 17.4% were outliers, with no cases managed with cystectomy. Of 929 hospitals that treated patients with PID, 9.9% were deemed outliers with low rates of guideline-adherent antibiotic administration. Low-volume hospitals were more likely to be outliers with low rates of use of methotrexate for ectopic pregnancy (6.7% of high-volume hospitals vs 49.7% of low-volume hospitals were outliers; adjusted odds ratio [aOR] 0.13, 95% CI, 0.05-0.31 for high-volume hospitals) and cystectomy for torsion (34.9% of low-volume vs 2.4% of high-volume hospitals were outliers; aOR 0.05, 95% CI, 0.01-0.18 for high-volume hospitals). There was no association between hospital volume and lower rates of guideline-based antibiotic use for PID. CONCLUSION: Higher hospital volume is associated with use of conservative, fertility-preserving treatment of emergency gynecologic conditions, including ectopic pregnancy and ovarian torsion.

The roles and limitations of robotic surgery for obese endometrial cancer patients: a common challenge in gynecologic oncology.

In the United States, the epidemic of obesity is readily apparent in women diagnosed with endometrial cancer, the most common gynecologic malignancy. Overall, the benefits of minimally invasive surgery and its oncologic outcomes are similar among laparoscopy and robotic approaches. However, in stratifying obese patients by BMI, more data is needed on morbidly obese patients and their candidacy for robotic surgery along with the technical challenges of staging procedures. Cost analysis studies targeted specifically to the obese and morbidly obese patient is needed to further justify efforts at promoting robotic surgery in this patient population.

A prospective comparison of postoperative pain and quality of life in robotic assisted vs conventional laparoscopic gynecologic surgery.

OBJECTIVE: We sought to compare robotic vs laparoscopic surgery in regards to patient reported postoperative pain and quality of life. STUDY DESIGN: This was a prospective study of patients who presented for treatment of a new gynecologic disease requiring minimally invasive surgical intervention. All subjects were asked to take the validated Brief Pain Inventory-Short Form at 3 time points to assess pain and its effect on quality of life. Statistical analyses were performed using Pearson x(2) and Student's t test. RESULTS: One hundred eleven were included in the analysis of which 56 patients underwent robotic assisted surgery and 55 patients underwent laparoscopic surgery. There was no difference in postoperative pain between conventional laparoscopy and robotic assisted surgery for gynecologic procedures. There was a statistically significant difference found at the delayed postoperative period when evaluating interference of sleep, favoring laparoscopy (ROB 2.0 vs LSC 1.0; P = .03). There were no differences found between the robotic and laparoscopic groups of patients receiving narcotics (56 vs 53, P = .24, respectively), route of administration of narcotics (47 vs 45, P > .99, respectively), or administration of nonsteroidal antiinflammatory medications (27 vs 21, P = .33, respectively). CONCLUSION: Our results demonstrate no difference in postoperative pain between conventional laparoscopy and robotic assisted surgery for gynecologic procedures. Furthermore, pain did not appear to interfere consistently with any daily activity of living. Interference of sleep needs to be further evaluated after controlling for bilateral salpingo-oophorectomy.

Routine cystoscopy after robotic gynecologic oncology surgery.

BACKGROUND AND OBJECTIVES: Our aim was to determine whether the use of routine cystoscopy increases lower urinary tract injury detection (bladder and/or ureter) after robotic surgery performed by gynecologic oncologists. METHODS: A retrospective chart review of patients who presented for robotic hysterectomy from 2009-2012 was performed at 2 separate academic medical centers, one that performed routine cystoscopy and one that did not. Statistical analysis was performed with t tests and χ2 tests. RESULTS: We identified 140 cases without cystoscopy and 109 cases with routine cystoscopy. There were no intraoperative or postoperative urinary injuries detected in either group. There were no significant differences in age and body mass index. In the non-cystoscopy group, a larger specimen size (P<.001), less blood loss (P=.013), and a longer mean operative time were observed (P<.0001). In the routine cystoscopy group, more lymphadenectomies were performed with hysterectomy (P=.007) and more patients underwent hysterectomy for ovarian cancer (P=.0192). There were no differences in surgical indications or secondary procedures including bilateral salpingo-oophorectomy, radical hysterectomy, ureterolysis, and pelvic organ prolapse-related procedures. The minimum follow-up period was 30 days in both groups. CONCLUSION: Routine use of cystoscopy did not appear to affect the detection rate of intraoperative lower urinary tract injury during robotic gynecologic surgery because this rate was zero in both groups. However, cystoscopy is relatively simple to perform and can be efficiently incorporated into robotic surgery to avoid the severe morbidity and possible litigation surrounding a urinary tract injury.

Two cases of post-coital vaginal cuff dehiscence with small bowel evisceration after robotic-assisted laparoscopic hysterectomy.

INTRODUCTION: Vaginal cuff dehiscence following robotic surgery is uncommon. Published reports of vaginal cuff dehiscence following robotic surgery are increasing, but the true incidence is unknown. PRESENTATION OF CASE: Case 1. A 45 year old female had sexual intercourse and presented with a vaginal cuff dehiscence complicated by small bowel evisceration 4 months after RA-TLH. Case 2. A 44 year old female had sexual intercourse and presented with a vaginal cuff dehiscence with small bowel evisceration 6 weeks after RA-TLH. DISCUSSION: We discuss the rate of vaginal cuff dehiscence by mode of hysterectomy, surgical and non-surgical risk factors that may contribute to vaginal cuff dehiscence, and proposed preventative methods at the time of RA-TLH to reduce this complication. CONCLUSION: Vaginal cuff dehiscence with associated evisceration of intraabdominal contents is a potentially severe complication of hysterectomy. We recommend counseling patients who undergo RA-TLH to abstain from vaginal intercourse for a minimum of 8-12 weeks.

Abdominal wall port site metastasis after robotically staged endometrial carcinoma: A case report.

INTRODUCTION: The incidence of port-site metastasis following robotic-assisted laparoscopic hysterectomy is unknown. PRESENTATION OF CASE: We present a case of a 78-year-old female diagnosed with an incidental grade 3 endometrial adenocarcinoma on a final hysterectomy specimen. She subsequently underwent a robotic staging surgery with a gynecologic oncologist where nodal pathology was found to be negative; her final stage was 1B. One year following diagnosis, she developed a recurrence on her abdominal wall at the former port-sites with concomitant vaginal cuff recurrence. DISCUSSION: We hypothesize possible modes of metastasis and present limited published data to date on port site metastasis following robotic hysterectomy for endometrial cancer. CONCLUSION: This is the second reported case of port-site metastasis following robotic surgery for endometrial cancer.

Grade 1 endometrioid endometrial carcinoma presenting with pelvic bone metastasis: a case report and review of the literature.

Most grade 1 endometrioid endometrial cancers are confined to the uterus at the time of diagnosis and confer a good prognosis. Rarely will a grade 1 endometrioid endometrial carcinoma present with distant metastasis, especially to the bone. We present the case of a 56-year-old woman with postmenopausal bleeding and right hip pain due to metastatic grade 1 endometrioid uterine cancer invading into the right ischium. We discuss treatment options as well as provide a review of prior published reports on bony metastasis in grade 1 endometrioid endometrial cancers. To date, this case is one of 10 others which demonstrates that even a well-differentiated, low-grade endometrioid endometrial carcinoma can progress in a highly aggressive manner.

Roles of LPA in ovarian cancer development and progression.

Lysophosphatidic acid (LPA), a bioactive phospholipid, stimulates survival, proliferation, adhesion, migration and invasion of ovarian cancer cells through the activation of G-protein-coupled plasma membrane receptors. LPA and its receptors are aberrantly expressed in ovarian cancer, with high levels predominantly found in malignant ascites and in the plasma of ovarian cancer patients. LPA signals multiple intracellular pathways, such as Ras/MEKK1-MAPK and PI3K/Akt, to promote growth factors and protease expression, and induce angiogenesis and tumor cell invasion through the extracellular matrix and across the basement membrane. Only a small portion of this intricate lipid-signaling cascade has been characterized thus far. We believe that elucidation of this complex transduction network will provide further opportunities to understand the mechanism of ovarian carcinogenesis, invasion and metastasis.

VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced epithelial ovarian cancer (EOC) invasion.

BACKGROUND: The VEGF-VEGF receptor (VEGFR) signaling axis has emerged as a promising target for cancer therapy, attributing to its vital role in tumor angiogenesis and growth. We have previously reported the regulation of epithelial ovarian cancer (EOC) invasion and migration by VEGF and the implication of VEGF-VEGFR-2 axis in lysophosphatidic acid (LPA)-induced EOC invasion. However, the expression profile of VEGF and VEGFRs in EOC, their association with tumor aggressiveness, and their regulation by LPA remain unclear. OBJECTIVES AND METHODS: In this study, we examined the expression of VEGFR-1, VEGFR-2, neuropilin-1 (NRP-1), NRP-2, VEGF(121), and VEGF(165) in established EOC cell lines and assessed their correlation with cell invasiveness. Moreover, using an ovarian cancer tissue qPCR array, we analyzed VEGFR-2 expression across a panel of 48 tissues with different disease stages and histological grades. We also tested the effect of LPA on VEGF and VEGFR-2 expression and examined whether blocking VEGFR-2 by RNA interference (RNAi) affects LPA-induced EOC invasion. RESULTS: We show that VEGF and VEGFR-2 expression correlates with cell invasiveness and VEGFR-2 expression in ovarian cancer tissues correlate with tumor grade. In addition, LPA, at 20 muM, significantly induced the expression of VEGF(121), VEGF(165), and VEGFR-2 in SKOV3 and DOV13 cells (P<0.05). VEGFR-2 small interference RNA (siRNA) transfection remarkably decreased LPA's invasion-promoting effect (P<0.001) in SKOV3 cells without significantly decreasing SKOV3 cells' basal invasiveness. In DOV13 cells, VEGFR-2 silencing significantly decreases both the basal level cell invasion and LPA's invasion promoting effect (P<0.001). CONCLUSION: These results suggest that decreasing VEGFR-2 expression by RNAi may prove to be an effective method to reduce the metastatic potential of EOC cells exposed to elevated levels of LPA.

Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced stage ovarian cancer: a case report.

BACKGROUND: Tuberculosis is still a common problem in immigrant population with peritoneal tuberculosis as the most common presentation of extrapulmonary disease. CASE: A 36-year-old woman presented with abdominal distention, night sweats and weight loss. Physical examination and radiologic studies revealed ascites, omental caking and bilateral enlarged ovaries with an elevated serum Ca-125 of 353 U/mL. Acid-fast stain and culture were negative for Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy revealed multiple granulomas with epithelioid cells and caseification necrosis confirming tuberculosis. Treatment with anti-tuberculin drugs resulted in resolution of symptoms with a reduction in Ca-125 to normal. CONCLUSION: Laparoscopic biopsy with frozen section evaluation would spare patients with peritoneal tuberculosis from unnecessary extensive surgery. Serum Ca-125 level may be useful in monitoring treatment response.