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The phase 2, multicohort, open-label LEAP-005 study evaluated lenvatinib plus pembrolizumab in patients with previously treated advanced solid tumors. We report outcomes from the ovarian cancer cohort. Eligible patients had metastatic/unresectable ovarian cancer and had received 3 previous lines of therapy. Patients received lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks. Treatment continued until progression, unacceptable toxicity, or (for pembrolizumab) completion of 35 cycles. Primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Thirty-one patients were enrolled. 39% had high grade serous ovarian cancer, 23% were platinum-sensitive, 55% were platinum-resistant, 23% were platinum-refractory, and 84% had tumors that had a PD-L1 combined positive (CPS) score ≥1. ORR (95% CI) was 26% (12%–45%) by investigator assessment and 35% (19%–55%) by blinded independent central review (BICR). Per BICR, median DOR was 9.2 (1.5+ to 37.8+) months. ORRs (95% CI) by BICR were 35% (9/26 patients; 17%–56%) for PD-L1 CPS ≥ 1 disease and 50% (2/4 patients; 7%–93%) for PD-L1 CPS < 1 disease. Median (95% CI) PFS by BICR and OS were 6.2 (4.0–8.5) months and 21.3 (11.7–32.3) months, respectively. Treatment-related AEs occurred in 94% of patients (grade 3–4, 77%). One patient died from treatment-related hypovolemic shock. Lenvatinib plus pembrolizumab demonstrated antitumor activity as fourth line therapy in patients with advanced ovarian cancer, and no unanticipated safety signals were identified. Responses were observed regardless of PD-L1 status. • We evaluated lenvatinib plus pembrolizumab as fourth-line therapy in 31 patients with advanced ovarian cancer. • Lenvatinib plus pembrolizumab had an objective response rate of 35% by blinded independent central review in this population. • Median duration of response by blinded independent central review was 9.2 (1.5+ to 37.8+) months. • Median progression-free survival was 6.2 months and median overall survival was 21.3 months. • Treatment-related adverse events occurred in 94% of patients (grade 3–4, 77%; grade 5, 3%). [ABSTRACT FROM AUTHOR]

The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLE mut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p =.003 and p =.001) and NSMP (p =.020 and p =.049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p =.033) and death (p =.008) in p53abn endometrial cancer patients. Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer. • Patients with p53abn endometrial cancer showed the highest rate of positive peritoneal cytology. • Positive peritoneal cytology is associated with worse oncological outcome in NSMP and p53abn endometrial cancer patients. • In women with p53abn endometrial cancer, positive peritoneal cytology is an independent predictor of recurrence and death. [ABSTRACT FROM AUTHOR]

Optimal management of obese patients with early-stage cervical cancer is debated despite evidence of non-inferior survival in obese patients undergoing radical hysterectomy with pelvic lymphadenectomy (RH) compared to primary radiation with or without radiosensitizing chemotherapy (RT). Objectives included describing patient factors affecting disposition to RH versus RT; comparing RH outcomes for obese (BMI >30 mg/m2) and non-obese patients; and comparing differences in recurrence free survival (RFS) and overall survival (OS). This was a single institution cohort study of all cervical cancer patients who underwent RH or were candidates for RH based on clinical stage. Demographic, clinicopathologic and treatment outcomes were collected and analyzed. RT patients (n = 39, 15%) had a higher BMI (p = 0.004), older age (p < 0.001), more life-limiting comorbidities (LLC) (p < 0.001), larger tumor size (p = 0.001), and higher clinical stage (p = 0.013) compared to RH patients (n = 221, 85%). On multivariable survival analysis there was no difference in OS based on treatment modality; significant predictors of worse OS were larger tumor size, higher number of LLC and recurrence. Among the RH group, obese patients had a longer operative time (p = 0.01) and more LLC (p = 0.02); there were no differences in demographic or clinicopathologic characteristics, operative outcomes, RFS or OS compared to non-obese patients. In this cohort of RH-eligible cervical cancer patients, BMI was independently associated with disposition to RT. Studies demonstrate that RH is feasible and safe in obese patients with no difference in RFS or OS when compared to non-obese patients. Thus, the decision for disposition to RT should not be based on obesity alone. • The preferred treatment of early-stage cervical cancer in patients with obesity is undefined. • Obesity is associated with disposition to primary radiation therapy in patients who are candidates for radical hysterectomy. • This study and previous have indicated safety and feasibility of radical hysterectomy in carefully selected obese patients. • Though radical hysterectomy in obese patients may be more technically difficult, outcomes are not different. • The decision for disposition to radiation therapy in early-stage cervical cancer should not be based on obesity alone. [ABSTRACT FROM AUTHOR]

An important question in determining long-term prognosis for women with ovarian cancer is whether risk of death changes the longer a woman lives. Large real-world datasets permit assessment of conditional survival (CS) given both prior overall survival (OS) and real-world progression-free survival (rwPFS). Using a longitudinal dataset from US oncology centers, this study included 6778 women with ovarian cancer. We calculated CS rates as the Kaplan-Meier probability of surviving an additional 1 or 5 years, given no mortality (OS) or disease progression (rwPFS) event in the previous 0.5–5 years since first-line chemotherapy initiation, adjusted for factors associated with OS based on multivariable Cox regression. Median study follow-up was 9 years (range, 1–44) from first-line initiation to data cutoff (17-Feb-2021). Median OS was 58.0 months (95% CI, 54.9–60.8); median rwPFS was 18.4 months (17.4–19.4). The adjusted 1-year CS rate (ie, rate of 1 year additional survival) did not vary based on time alive, whereas the adjusted 5-year CS rate increased from 48.5% (47.0%–50.1%) for women who had already survived 6 months to 66.4% (63.3%–69.6%) for those already surviving 5 years (thus surviving 10 years total). The adjusted 1-year CS rate increased from 90.4% (89.5%–91.4%) with no rwPFS event at 6 months to 97.6% (96.4%–98.8%) with no rwPFS event at 5 years; adjusted 5-year CS rate increased from 53.7% (52.0%–55.5%) to 85.0% (81.2%–88.9%), respectively. This analysis extends the concept of CS by also conditioning on time progression-free. Patients with longer rwPFS experience longer survival than patients with shorter rwPFS. • Women with ovarian cancer have an increasing probability of survival with increasing time survived after the diagnosis. • Conditional survival (CS) is the probability of surviving + y years, given already having survived x years post-diagnosis. • The 5-year CS rate increased from 54% for survival with no disease progression at 6 mos to 85% with no progression at 5 yrs. • The prognosis for ovarian cancer improved substantially with time for women alive without disease progression. [ABSTRACT FROM AUTHOR]

We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based chemotherapy (PC) for endometrial cancer (EC). A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test. Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25–3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01–4.18, p = 0.04). In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients. • Many patients will use antibiotics and/or a proton pump inhibitor at time of adjuvant therapy for endometrial cancer. • PPI use at time of adjuvant platinum-based chemotherapy is independently associated with worse outcomes. • Antibiotic use at time of adjuvant platinum-based chemotherapy was associated with worse survival on univariate analysis. [ABSTRACT FROM AUTHOR]

Prior studies have demonstrated survival differences between Black women with endometrial cancer (EC) born in the US and Caribbean. Our objective was to determine if country of birth influences EC overall survival (OS) in disaggregated subpopulations of Black women. Using the Florida Cancer Data System, women with EC diagnosed from 1981 to 2017 were identified. Demographic and clinical information were abstracted. Women who self-identified as Black and born in the US (USB), Jamaica (JBB), or Haiti (HBB) were included. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods with significance set at p < 0.05. 3817 women met the inclusion criteria. Compared to USB, JBB and HBB had more high-grade histologies, more advanced stage disease, had a greater proportion of uninsured or Medicaid insured, and had a higher proportion of women who received chemotherapy (all p < 0.05). In multivariate analyses, age (HR 1.03 [1.02–1.05]), regional stage (HR 1.52 [1.22–1.89]), distant stage (HR 3.73 [2.84–4.89]), lymphovascular space invasion (HR 1.96 [1.61–2.39]), receipt of surgery (HR 0.47 [0.29–0.75]), and receipt of chemotherapy (HR 0.77 [0.62–0.95]) were independently associated with OS. Compared to USB, Haitian nativity was an independent negative predictor of OS when evaluating all histologies together (HR 1.54 [1.18–2.00]) and for endometrioid EC specifically (HR 1.77 [1.10–2.83]). Among women with serous EC, HBB had markedly worse median OS (18.5 months [13.4–46.5]) relative to USB (29.9 months [26.3–35.9]) and JBB (41.0 months, [34.1–82.6], p = 0.013). Country of birth is associated with endometrial cancer survival in Black women, with HBB demonstrating worse outcomes. • Intra-racial disaggregation provides additional insight into health disparities found in women with endometrial cancer (EC). • Jamaican and Haitian-born Black women in the US have higher rates of high-grade EC than US-born Black women. • Haitian-born Black women in the US with serous EC experience worse overall survival than women born in Jamaica and the US. [ABSTRACT FROM AUTHOR]

The dependent coverage mandate in the 2010 Affordable Care Act (ACA) allows young adults to stay on a parent's private insurance through age 26. While this mandate is associated with gains in insurance and early-stage cancer diagnosis, its long-term impact on survival is unknown. To compare insurance coverage, stage at diagnosis, and overall survival in patients with gynecologic cancer before and after the ACA's dependent coverage mandate. Using difference-in-differences (DiD) analysis, we conducted a retrospective cohort study comparing outcomes before and after the implementation of the ACA's dependent coverage mandate in young patients with gynecologic cancer, ages 18–26 years (exposure group) to patients ages 27–35 (control group). We analyzed insurance coverage, stage at diagnosis, and 1, 2, and 3-year overall survival, adjusted for age and comorbidities, utilizing the 2004–2017 National Cancer Database. IRB exemption was obtained. A total of 3553 cases pre-reform and 4535 cases post-reform were identified for patients 18–26 years compared to 14,420 pre-reform and 19,821 post-reform for patients age 27–35. The ACA's dependent coverage mandate was associated with significant gains in insurance (DiD 2%, 95% CI 0.6–3.5) and early-stage diagnosis (3.1%, 95% CI 0.6–5.7). The ACA's dependent coverage mandate was associated with significant gains in 3-year survival (2.4%, 95% CI 0.4–4.3) and non-significant gains in 1 and 2-year survival. The ACA's dependent coverage mandate is associated with improvements in early-stage diagnosis and survival for young patients with gynecologic cancer. Maintaining insurance gains—and expanding to the remaining uninsured—are critical for the health of young patients with gynecologic cancer. • The Affordable Care Act's dependent coverage mandate was associated with long-term gains in insurance coverage and early-stage cancer diagnosis. • The ACA's dependent coverage mandate was associated with improved 3-year survival for young patients with gynecologic cancer. • Expansion of insurance coverage to the remaining 29 million uninsured may improve cancer outcomes. [ABSTRACT FROM AUTHOR]

We assessed a conditional probability of survival (CPS) model to determine the probability of living 10 years after ovarian cancer diagnosis after having already survived 5 years. We identified patients newly diagnosed with high-grade epithelial ovarian cancer from 1/1/2001–12/31/2009 and treated at our institution. Patients with <3 years follow-up were excluded. CPS was defined as the probability of surviving additional years (y) based on the condition a patient had already survived a given time (x): S (x + y)/ S (x). Confidence intervals were estimated using a variation of Greenwood's formula. Of 916 patients meeting inclusion criteria, 473 (52%) were diagnosed from 2001 to 2005 and 443 (48%) from 2006 to 2009. Median age at diagnosis was 60 years (range, 25–95). The conventional 10-year OS rate for all patients was 29% (95% CI: 26%–32%)—75% (95% CI: 68%–82%) for stage I/II disease, 22% (95% CI: 19%–26%) for stage III, and 6.9% (95% CI: 3.9%–12%) for stage IV. For patients <65 years, the 10-year CPS for 5-year survivors was 65% (95% CI: 59%–70%); for those ≥65 years, it was 48% (95% CI: 38%–57%). For patients <65 years, the 10-year CPS for 5-year survivors by stage was: stage I/II, 89% (95% CI: 81%–94%); stage III, 58% (95% CI: 50%–66%); and stage IV, 26% (95% CI: 12%–42%). For patients ≥65 years, rates by stage were 78% (95% CI: 53%–91%), 42% (95% CI: 30%–53%), and 29% (95% CI: 7%–56%), respectively. For long-term survivors with high-grade epithelial ovarian cancer, CPS provides better prediction of survival than conventional methods. • Traditional 5-year overall survival rates do not account for changes in survival probability over time. • For survivors with ovarian cancer, survival probability strongly depends upon the amount of time elapsed since diagnosis. • Ten-year conditional probability of survival (CPS) gives a more accurate prediction of survival than conventional methods. • CPS can be utilized to benefit patient counseling and prospective trial planning. [ABSTRACT FROM AUTHOR]

The objective of this study is to externally validate the KELIM (rate of elimination of CA-125 elimation) score in patients with high grade serous ovarian cancer(HGSC)undergoing NACT and determine its relation to outcome of cytoreduction, platinum sensitivity, progression free(PFS) and overall survival(OS). This is a retrospective cohort study of patients with Stage III-IV HGSC diagnosed between January 1, 2010 and December 31, 2019 and treated with NACT. KELIM score was calculated using at least 3 CA-125 values within the first 100 days of chemotherapy. Demographic parameters were collected and Kaplan Meier survival analyses were performed for PFS and OS. This study was approved by local ethics board. 217 patients met inclusion criteria. Median follow-up was 28.93 months(range 2.86–135.06). There was no significant difference in stage, functional status, cytoreductive outcome or BRCA status(germline or somatic) between patients with a KELIM ≥ 1 and <1. Patients with a KELIM<1 had a lower median PFS (13.58 vs 19.69, p < 0.001), median platinum free interval(PFI) (7.66 vs 13.64, p < 0.001) and 5-year OS (57% vs 72%, p = 0.0140) compared to patients with KELIM≥1. After adjusting for stage, treatment delays, bevacizumab or poly adenosine diphosphate-ribose polymerase(parp)-inhibitor use, and BRCA status, patients with KELIM<1 had a high risk of disease progression(HR = 1.57 (95% CI 1.08–2.28) and death(HR = 1.99 (95% CI 1.01–3.95) compared to KELIM≥1. BRCA status was independently associated to an increase on KELIM score (OR = 1.917, 95% CI 1.046–3.512, p = 0.035). Patients with advanced HGSC undergoing NACT with a KELIM <1 were more likely to have platinum-resistant disease, worse PFS and worse OS when compared to patients with KELIM≥1. The KELIM score can be a helpful tool to predict chemo-response and aid in treatment decision making. • KELIM score may be a marker of chemosensitivity in patients with ovarian cancer treated with neoadjuvant chemotherapy. • Patients with a KELIM<1 had a lower progression free- and overall survival compared to patients with KELIM ≥1. • Patients with KELIM<1 had higher risk of disease progression and death compared to patients with KELIM ≥1. • BRCA positive mutation status was independently associated with a higher KELIM score. • Patients with KELIM<1 were more likely to have platinum-resistant disease and worse progression free- and overall survival. [ABSTRACT FROM AUTHOR]

To determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer. Data were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy. Of 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99). The prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits. • Risk calculator redefines prognosis in early stage high risk epithelial ovarian cancer. • Cohort of patients identified by the calculator may not benefit from adjuvant treatment. • A simplified calculator of age, stage, histology, and grade is also predictive of treatment benefit. [ABSTRACT FROM AUTHOR]

We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS). We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual <1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany. A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival. The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm. • The size of residual tumors after surgery is evaluated surgically and radiologically for advanced ovarian cancer (AOC). • The incorporation of the two assessments is more accurate to predict prognosis of optimal debulked, high-grade serous AOC. • No gross residual on postoperative CT shows better survival in patients optimal debulked, high-grade serous AOC. [ABSTRACT FROM AUTHOR]

Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%–44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675–0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients. • The 5-year post-recurrence disease-specific survival (PR-DSS) rate was 39.1% in patients with early-stage cervical cancer. • The strongest factors for PR-DSS were primary tumour size and the presence of symptoms at diagnosis of recurrence. • The presence of symptoms at recurrence remained a significant prognostic factor after correction for lead-time bias. • PR-DSS was best in patients without LN involvement or LVSI suffering from solitary asymptomatic recurrence. [ABSTRACT FROM AUTHOR]

To report 20-year trends in incidence and survival of vulvar cancer in Korea. Using data from the Korean Central Cancer Registry, age-standardized incidence rates (ASRs) and annual percentage changes (APCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method, and conditional net survival (CNS) was calculated. A total of 2221 patients was diagnosed with vulvar cancer during the 1999–2018 period, with an ASR of 0.32 per 100,000 person-years. Among the cases, 51.4% were squamous cell carcinoma (SqCC), 21.3% were Paget disease, and 8.6% were basal cell carcinoma (BCC). There was an increase in incidence for all vulvar cancer (APC 2.4%, 95% CI 1.8–3.0). However, although BCC (APC 7.0%, 95% CI 3.3–10.8) and Paget disease (APC 5.9%, 95% CI 4.2–7.6) increased, SqCC did not (APC 0.2%, 95% CI -0.8–1.2). There was an increase in incidence in all age groups. The 5Y NS was 74.0% overall, and it did not improve significantly during the study period. The 5Y CNS of vulvar cancer increased continuously with time survived: from 74.0% (71.4–76.4) at baseline to 98.1% (95% CI, 85.4–99.8) at 5 years after diagnosis. The incidence of vulvar cancer in Korea showed a different pattern from those in the US and Europe: SqCC incidence was relatively low and remained stable, but the incidence of BCC and Paget's disease increased. Survival did not improve in the past two decades. Patients can be considered cured after surviving for 5 years. • The incidence of vulvar cancer in Korea showed a different pattern from those in the US and Europe • Incidence of squamous cell carcinoma incidence was relatively low and remained stable • Incidence of basal cell carcinoma and Paget's disease increased. • Survival did not improve in the past two decades. • Patients can be considered cured after surviving for 5 years. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) with laparoscopic (LAP) or laparotomic (OPEN) radical hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN were reported. Results: There were 6,477 unique references identified from initial search, from which 27 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =670) versus LAP (n =1057) was 1.12 (95% CI:0.87-1.44; p=0.39; I2=0%), and ROBOT (n =3320) versus OPEN (n =11,991) was 1.13 (95% CI:0.89-1.44; p=0.31; I2=47%). The weighted HR for OS for ROBOT (n =746) versus LAP (n =1082) was 1.01 (95% CI: 0.56-1.80; p=098; I2=46%) and ROBOT (n =3945) versus OPEN (n =13,050) was 1.18 (95% CI: 0.99-1.41; p=0.06; I2=32%). Conclusions: Compared to OPEN and LAP radical hysterectomy, the studies show that ROBOT radical hysterectomy does not result in worse oncologic outcomes with respect to DFS and OS. The noted outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/ S (x). Confidence intervals (CIs) were estimated using a variation of Greenwood's formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS. [ABSTRACT FROM AUTHOR]

Objectives: To compare overall survival (OS) in women with endometrial cancer who received hysterectomies with and without oophorectomies. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results Program (SEER) Research Plus dataset. The sample included endometrial cancer women aged 18 and above diagnosed between 2014 to 2018 (n =52,680) who had hysterectomies with oophorectomies (ovary removed) and without oophorectomies (ovary retained). Histology of endometrial cancer included low-grade and high-grade endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma, carcinosarcoma, and mixed type. Kaplan-Meier curves, log-rank comparisons, and Cox regression analyses were used to evaluate OS. Results: There were 97.4% patients (n =51,324) who had oophorectomies while 2.6% (n =1,356) did not. Mean age was 62.7 years; the majority were White (79.6%, n =41,941), stage I (78.8%, n =41,496), and endometrioid type (78.1%, n =41,142). Adjuvant therapies were radiation (28.3%, n =14,893), chemotherapy (22.6%, n =11,930), and combined radiation/chemotherapy (12.5%, n =6,598). There were 5,051 deaths (9.6%) among which 119 deaths (0.2%) were in the ovary retained group while 4,943 deaths (9.4%) were in the ovary removed group. In the whole sample, OS did not differ between the two groups (p=0.14). In those with late-stage endometrial cancer (stages III and IV), there were lower hazards for OS (HR:0.75, 95% CI: 0.58-0.97, p=0.03) in the ovary removed group. In those with early-stage endometrial cancer (stages I and II), the OS did not differ between the two groups (p=0.21). Conclusions: Oophorectomy in late-stage endometrial cancer patients who received hysterectomy was associated with improved OS. However, oophorectomy in early-stage endometrial cancer patients was not associated with improved OS. Fertility-sparing surgery may be considered for those in early-stage endometrial cancer who desire to preserve ovary function. Further studies are needed to confirm when oophorectomy is indicated in endometrial cancer patients with ovarian activity. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a nomogram for the overall survival of epithelial ovarian cancer based on the National Union of Real- World Gynecological Oncology Research and Patient Management Platform (NUWA) in China. Methods: We enrolled patients with pathologically confirmed primary epithelial ovarian cancer in the NUWA platform between 2004 and 2018 as a training cohort to develop a nomogram. The cut-off for follow-up was December 2020. Patients with a history of other tumors or missing values of any variable were excluded. Variables were selected by univariate and multivariate Cox proportional hazard regression. Significant factors were applied to establish a nomogram to predict 3-year and 5-year survival, assessed by C-statistic and calibration curves. A testing cohort from SEER Database was applied to externally validate the nomogram by bootstrap resampling. Statistical analysis was conducted by SPSS version 26.0 (IL, USA) and R version 4.1.1 (www.r-project.org). Results: A total of 1262 primary epithelial ovarian cancer patients were filtered out from 5003 ovarian cancer patients in the NUWA platform. Total 10594 of 125682 patients in the SEER Database were screened out accordingly. Baseline age, histotype, histological grade, FIGO stage, longest diameter of the primary tumor, and residual disease after primary surgery were significant risk factors (p <0.05). Compared with serous cancer, the hazard ratio (HR) of mucinous, endometrioid, clear cell, other epithelial cancer were 3.391 (95% CI: 2.201-5.223), 1.642 (95% CI: 1.045-2.580), 3.127 (95% CI: 2.134-4.582), and 2.071 (95% CI: 1.486-2.885), respectively. The HR of advanced stage and high grade of disease (FIGO stage III-IV vs I-II, High grade vs Low/moderate grade) were 1.921 (95% CI: 1.226-3.010) and 1.407 (95% CI: 1.048-1.889), respectively. Patients who received optimal (R1), suboptimal (R2) cytoreduction, and those who didn't receive primary debulking surgery had a higher risk of death compared to those without the residual disease (R0), with HRs of 5.530 (95% CI: 3.575-8.555), 7.757 (95% CI: 5.101-11.796) and 9.975 (95% CI: 5.831-17.063), respectively. For continuous variables, the HR of baseline age (years) was 1.024 (95% CI: 1.013-1.036), and the HR of the longest diameter of the primary tumor (cm) was 1.030 (95% CI: 1.007-1.054). The C-statistic values of the nomogram (Figure 1) in the training and testing cohorts were 0.771 (95% CI: 0.748-0.794) and 0.726 (95% CI: 0.718-0.734), respectively. The slopes of calibration curves of 3-year and 5-year survival in the training cohort were 1.165 (95% CI: 0.990-1.340) and 0.955 (95% CI: 0.920-0.990), respectively, whereas, in the testing cohort, these were 1.355 (95% CI: 1.108-1.602) and 1.374 (95% CI: 1.103-1.644), respectively. [Display omitted] Conclusions: The discrimination and goodness of fit of the nomogram indicated its predictive value for the survival of epithelial ovarian cancer in China. Furthermore, the nomogram also obtains certain values in external validation, which implies its feasibility in different populations. [ABSTRACT FROM AUTHOR]

Objectives: To compare long-term oncologic outcomes of robotic- assisted (ROBOT) procedures with laparoscopy (LAP) and laparo- tomic (OPEN) hysterectomy based on comparative studies in the published literature. Methods: A systematic literature review and meta-analysis for timedependent oncologic outcomes were conducted in accordance with the PRISMA statement, the Cochrane guidelines and registered with PROSPERO. PubMed, Scopus, and Embase databases were searched. Studies included those comparing robotic to non-robotic hysterectomy with 20 or more cases for each comparator from January 1, 2010, to September 1, 2020. Additionally, studies needed to report on hysterectomy for cancer, distinguish robotic from non-robotic cases, with a minimum follow-up of 12 months or more, and report at least one outcome of interest; disease-free/recurrence-free (DFS) or overall survival (OS). A hierarchical decision tree was developed to calculate and combine hazard ratios (HR) based on information available in each paper, maximizing the number of studies for consideration. Comparisons of long-term oncologic results for ROBOT versus OPEN and LAP were reported. Results: There were 6,477 unique references identified from initial search from which 19 studies were included based on an adjusted analysis of HRs with heterogeneity tests. The weighted HR for DFS for ROBOT (n =1152) versus LAP (n =1029) was 0.94 (95% CI: 0.71-1.26; p=0.68; I2=0%), and ROBOT (n =887) versus OPEN (n =1035) was 0.84 (95% CI: 0.64-1.11; p=0.22; I2=0%). The weighted HR for OS for ROBOT (n =4675) versus LAP (n =2643) was 0.98 (95% CI: 0.82-1.16; p=0.78; I2=0%) and ROBOT (n =27,647) versus OPEN (n =23,923) was 0.77 (95% CI: 0.71-0.83; p<0.0001; I2=18%). Conclusions: When compared with OPEN and LAP hysterectomy, ROBOT hysterectomy does not result in worse oncologic outcomes with respect to DFS and shows improved OS results compared to OPEN. The noted improved outcomes with ROBOT need further validation and investigation. [ABSTRACT FROM AUTHOR]

Objectives: Therapy for early-stage epithelial ovarian cancer (EOC) involves complete surgical staging with or without adjuvant chemotherapy. The current international multi-center study aimed to investigate the long-term survival of different histological subtypes for stage I EOC. Methods: A multi-center cohort study was performed among all patients with FIGO stage I (IA-IC3) EOC treated at four European referral centers between 1985 and 2021. Overall survival (OS) and progression-free (PFS) survival were compared between the different stage I groups using Kaplan-Meier survival curves. Results: A total of 1115 patients met the inclusion criteria. Of them, 48.4% (n =540) were in stage IA, 6.6% (n =73) stage IB, and 45% (n =502) stage IC: stage IC1 54% (n =271), stage IC2 31.5% (n =158), and stage IC3 14.5% (n =73). The predominant histologic subtypes included highgrade serous (25.4%), low-grade endometrioid (24.8%), and clear cell (19%). Complete surgical staging, including lymphadenectomy, was performed in 62.1%, and 60% received adjuvant platinum-based chemotherapy. The median follow-up was 48 months. The median five-year (5y) OS and PFS rates were 94% and 86%, respectively, with no difference between stage IA and IB. However, a significantly better OS and PFS were observed for stage IA as compared to stage IC (p=0.007 and p<0.001, respectively). Considering histologic subtypes, a significant better PFS was documented for low-grade mucinous and low-grade endometrioid subgroup (HR: 0.22; 95% CI: 0.09-0.45, p=0.001; HR: 0.49; 95% CI: 0.29-0.83, p=0.007, respectively), as well a better OS for the latter (HR: 0.43; 95% CI: 0.22-0.86, p=0.017). In stage IA-B, the different histology subtypes showed a comparable prognosis (5y: OS: 96% and PFS: 92%), with the exception of a worsened OS for high-grade mucinous cases (HR: 5.90; 95% CI: 1.55-22.4, p=0.009). Among stage IC, the histologic subgroups showed comparable OS (5y 92%), but significantly better PFS for low-grade mucinous and low-grade endometrioid subtypes (HR: 0.21; 95% CI: 0.05-0.86, p=0.031; HR: 0.44; 95% CI: 0.23-0.84, p=0.013, respectively). In the subgroup of high-grade serous ovarian cancer patients in stage IC disease, the chemotherapy with carboplatin/paclitaxel seems to be superior compared to single-agent platinum (5y OS: 100% vs 83%; p=0.009). In multivariate analysis, partial staging procedure (compared to complete) was found as risk factor for worsen PFS (HR: 1.73; 95% CI: 1.13-2.66, p=0.012), while low-grade endometrioid histology (compared to high-grade serous) showed better outcome regarding OS (HR: 0.46; 95% CI: 0.22-0.95, p=0.036) and PFS (HR: 0.42; 95% CI: 0.25-0.73, p=0.002). Conclusions: Overall, stage I ovarian cancer patients treated in referral centers exhibited an excellent prognosis regardless of the histologic type. Histologic subtype and quality of surgical treatment affect the prognosis. Our data suggest platinum-based combination chemotherapy for the subgroup of FIGO stage IC high-grade serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the interaction between pathologic and histologic features and impact on overall survival (OS) among patients with endometrial cancer classified by the four molecular subtypes, identified by The Cancer Genome Atlas (TCGA). Methods: Using TCGA's Pan-Cancer Atlas accessed via the cBioPortal, we identified patients with endometrioid or serous endometrial cancer. Patients with available molecular data were included in our analysis. We recorded available outcomes data, and FIGO stage and pathologic factors were manually extracted from surgical pathology reports. OS was compared among groups using Kaplan-Meier curves. Results: A total of 507 patients with molecularly subtyped endometrioid or serous endometrial cancers were identified. FIGO stage was inferred using surgical pathology reports, and data regarding LVSI and histologic grade were available in 467 patients. Tumors were categorized as POLE hypermutated (43/467; 9.2%), microsatellite instable (MSI) hypermutated (139/467; 29.8%), copy number low (CN-low) (142/467; 30.4%), and CN-high (143/467; 30.6%). While molecular subtype was significantly correlated with OS among the entire study population (p <0.0001), this correlation was only significant among stage III tumors when divided by FIGO stages (n =100, p = 0.012). Increasing histologic grade was associated with worse OS among patients with CN-low tumors (5-year survival: G1 100%, G2 88%, G3 59.4%; p = 0.0051) but not among patients with other TCGA molecular subtypes or low-grade tumors. Of the 73 patients with CN-high tumors with LVSI, 32 (43.8%) were node-positive. Of the 35 patients with CN-low tumors with LVSI, four (11.4%) were node-positive. The presence of LVSI was associated with worse OS than those without LVSI among patients with CN-high (3-year survival rate: 56.9% vs 83.1%, p = 0.0048) and CN-low (3-year survival rate: 88.5% vs 94.4%, p = 0.0024) tumors. Conclusions: In this cohort of patients with endometrioid and serous endometrial cancer from the TCGA, the presence of LVSI was associated with worse OS among patients with CN-low and CN-high tumors. Patients with CN-low tumors with LVSI were less likely to be node positive than patients with CN-high tumors with LVSI. Increasing histologic grade was associated with worse OS only among patients with CN-low tumors. These data support a combined molecular histopathologic classification for prognosis in endometrial cancer. [ABSTRACT FROM AUTHOR]

Objectives: Surgery is the mainstay of treatment for early-stage vulvar cancer. Adjuvant radiation is thought to improve survival for patients with positive margins; however, recent studies have called this into question. We aimed to evaluate the association of adjuvant radiation and margin status with overall survival in a contemporary cohort. Methods: A retrospective cohort study was performed among women with vulvar cancer identified from the National Cancer Database between 2004 and 2017. Patients with stage I and II disease, with a tumor diameter ≤4cm, and squamous histology who underwent lymph node assessment were included. Bivariable tests were used to examine associations. Cox proportional hazard regression was used to evaluate the effect of adjuvant radiation on overall survival. Results: Of 9,567 patients with early-stage squamous vulvar cancer who underwent lymph node assessment, 7.4% had positive margins (n = 709). Among those with positive margins, 27.9% received adjuvant radiation. Receipt of adjuvant radiation was not associated with older age, non-White race, or lack of insurance; however, it was associated with stage II disease (32.8% vs 20.0%), higher grade (21.7% vs 15.1%), and lymph vascular space invasion (18.8% vs 11.7%, all p<0.04). Moreover, receipt of adjuvant radiation was not associated with improved overall survival in patients with positive margins (HR: 1.01, 95% CI: 0.73-1.40). This did not change after adjustment for stage, grade, and presence of lymph vascular space invasion (HR: 0.70, 95% CI: 0.43-1.16). Conclusions: Adjuvant radiation did not improve overall survival in patients with early-stage squamous vulvar cancer and positive margins. [ABSTRACT FROM AUTHOR]