Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.

BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. RESULTS: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively. CONCLUSION: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03517449.

Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE-826.

Pembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double-blind, placebo-controlled KEYNOTE-826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD-L1 combined positive score (CPS) ≥1, all-comers, and PD-L1 CPS ≥10. Fifty-seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD-L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16-0.77]), all-comers (n = 57; 0.45 [0.22-0.90]), and patients with PD-L1 CPS ≥10 (n = 25; 0.36 [0.12-1.07]). HRs (95% CI) for OS were 0.38 (0.14-1.01), 0.41 (0.17-1.00), and 0.37 (0.10-1.30), respectively. Incidence of grade 3-5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE-826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer.

Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: Results from Study 309/KEYNOTE-775.

Study 309/KEYNOTE-775 is a phase 3 open-label, randomized trial of lenvatinib plus pembrolizumab versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer with progression after platinum-based therapy. Primary endpoints of superiority for lenvatinib plus pembrolizumab were met for progression-free survival (PFS) and overall survival (OS) in all-comers (ie, regardless of mismatch repair [MMR] status) and patients with MMR proficiency (pMMR). We present results for the Japanese subset. Patients were randomized to oral lenvatinib 20 mg/day plus intravenous pembrolizumab 200 mg every 3 weeks (Q3W; up to 35 cycles of pembrolizumab) or TPC (intravenous doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 QW [3 weeks on/1 week off]). Primary endpoints were PFS by blinded independent central review per RECIST version 1.1 and OS. One hundred four patients were randomized in Japan (data cutoff, October 26, 2020; median follow-up, 11.8 [range, 1.1-26.9] months). Hazard ratios (HRs) for PFS with lenvatinib plus pembrolizumab versus TPC were 1.04 (95% CI, 0.63-1.73) in patients with pMMR and 0.81 (0.50-1.31) in all-comers. Hazard ratios for OS were 0.74 (0.41-1.34) with pMMR and 0.59 (0.33-1.04) for all-comers. Adverse events were manageable and led to discontinuation of one/both study drugs in 36.5% of patients in the lenvatinib plus pembrolizumab group versus 7.8% in the TPC group. Similar to the global Study 309/KEYNOTE-775 results, this analysis suggested favorable efficacy and manageable safety with lenvatinib plus pembrolizumab after platinum-based chemotherapy in Japanese patients with advanced endometrial cancer and supports this combination as a new standard of care in this population.

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079).

OBJECTIVE: This multicenter, open-label, phase II study aimed to evaluate the efficacy and safety of paclitaxel-carboplatin, bevacizumab, and bevacizumab-based maintenance therapy for metastatic, recurrent, and persistent uterine cervical cancer. METHODS: Patients with measurable diseases that were not adapted to regional therapies, such as surgery or radiotherapy, and were systematic chemotherapy-naïve were eligible. The participants received paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) every three weeks until disease progression or unacceptable adverse events occurred. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), overall survival (OS), safety, and time to treatment failure. RESULTS: Sixty-nine patients were analyzed using our protocol. The median paclitaxel- carboplatin therapy duration was six cycles; 40% of patients received bevacizumab maintenance therapy. The median PFS was 11.3 months. The median OS was not reached; the median time to treatment failure was 5.9 months. The ORR was 79.7% [95% confidence interval (CI) 63.8-88.4]; 16 patients (23.2%) showed complete response (CR) and 39 patients (56.5%) showed partial response (PR). The median PFS was 14.3 months (95% CI 7.3-17 months) for the 25 patients who received maintenance therapy and 7.4 months (95% CI 6.1-11 months) for nonrecipients (p = 0.0449). Gastrointestinal perforation/fistulas occurred in four patients (5.6%), all of whom had a history of radiation therapy. CONCLUSIONS: Paclitaxel-carboplatin and bevacizumab therapy is an acceptable and tolerable treatment for advanced or recurrent cervical cancer.

A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082).

BACKGROUND: The standard treatment for stage IB-IIB cervical cancer is radiotherapy or radical hysterectomy; after radical hysterectomy, adjuvant concurrent chemoradiotherapy is recommended for patients with high risk factors. However, adjuvant concurrent chemoradiotherapy can cause severe gastrointestinal and urinary toxicity. PRIMARY OBJECTIVE: To assess whether postoperative adjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival in patients with high risk cervical cancer. STUDY HYPOTHESIS: Adjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival and will reduce severe toxicities. TRIAL DESIGN: Patients with high risk factors after radical hysterectomy will be randomized 1:1 to receive adjuvant concurrent chemoradiotherapy or adjuvant chemotherapy. Treatment will be started within 6 weeks of surgery. The concurrent chemoradiotherapy group will receive whole pelvis irradiation (50.4 Gy) and cisplatin (40 mg/m2/week). The chemotherapy group will receive paclitaxel (175 mg/m2) plus cisplatin (50 mg/m2) or carboplatin (AUC=6) every 3 weeks for six cycles. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients with high risk stage IB-IIB cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma) who underwent radical hysterectomy are eligible for the study. High risk is defined as the presence of pelvic lymph node metastasis and/or parametrial invasion. PRIMARY ENDPOINT: The primary endpoint is overall survival. SAMPLE SIZE: 250 patients in total are required. ESTIMATED DATES FOR COMPLETING ACCRUAL: This study began in November 2019, and 250 patients will be accrued within 5 years. TRIAL REGISTRATION NUMBER: The study has been registered with the Japan Registry of Clinical Trials (jRCTs041190042).

Comparison of pregnancy outcomes between women with early-onset and late-onset gestational diabetes in a retrospective multi-institutional study in Japan.

AIMS/INTRODUCTION: To compare pregnancy outcomes between women with gestational diabetes mellitus (GDM) diagnosed early and late in pregnancy in Japan. MATERIALS AND METHODS: We examined women diagnosed with GDM in this multi-institutional retrospective study. Women were divided into two groups by gestational age at diagnosis: <24 weeks of gestation (early group, 14.4 ± 4.2 weeks) and ≥24 weeks of gestation (late group, 29.6 ± 3.4 weeks). Dietary counseling with self-monitoring of blood glucose with or without insulin therapy was initiated for both groups. Pregnancy outcomes were compared between the groups. RESULTS: Data from 600 early and 881 late group participants from 40 institutions were included. Although pre-pregnancy body mass index was higher in the early group than in the late group, gestational weight gain was lower in the early group. Hypertensive disorders of pregnancy and cesarean section were more prevalent in the early than in the late group (9.3% vs 4.8%, P < 0.001; 34.2% vs 32.0%, P < 0.001, respectively). The prevalence of large-for-gestational-age infants was higher in the late than in the early group (24.6% vs 19.7%, respectively, P = 0.025). There was no significant difference in other neonatal adverse outcomes between the groups. Multiple logistic regression analysis showed that early group, nulliparity and pre-pregnancy body mass index were associated with hypertensive disorders of pregnancy. CONCLUSIONS: These results suggest that maternal complications, including hypertensive disorders of pregnancy and cesarean delivery, were higher in the early group than in the late group. Earlier intervention for GDM might be associated with a reduction in large-for-gestational-age infants.

Assessment of laparoscopic training for gynecological malignancies using Thiel-embalmed human cadavers.

The introduction of laparoscopic surgery has also been beneficial for patients with gynecological malignancies. In this respect, surgeons should receive related training in the context of human resource development. Hands-on training was introduced using Thiel-embalmed human cadavers (THCs) in 2014. To determine the usefulness of THCs, they were evaluated in terms of tissue color, consistency and operative tactility, among others, compared with in vivo laparoscopic training for gynecological malignancies. Hands-on training sessions using THCs were held for a total of 11 times at Ehime University Graduate School of Medicine between March 2014 and October 2017. Training on THCs included advanced laparoscopic procedures for radical hysterectomy type III. At the end of each training session, data were collected using a standardized, anonymous questionnaire termed the Likert scale. THCs ensured flexibility and plasticity of tissues and organs; therefore, the working space was similar to that in the living body under pneumoperitoneum. After analyzing the quality and consistency of tissue and organ color compared with in vivo conditions, most of the participants agreed or strongly agreed regarding the uterus, adnexa and ureter, but not regarding the large blood vessels. The highest scores were observed in the authenticity of the anatomical condition of each organ. Most participants strongly agreed that training using THCs would help improve their laparoscopic skills with a high level of satisfaction. Furthermore, most participants reported that they would recommend this training to other obstetrician-gynecologists. Laparoscopic training for gynecological malignancies using THCs was comparable to the in vivo conditions in terms of surgical view and operative tactility. Therefore, THCs may be an excellent training tool for improving laparoscopic surgical skills for gynecological malignancies.

Review of Treatment and Prognosis of Stage IVB Cervical Carcinoma.

OBJECTIVES: In most patients, stage IVB cervical cancer is incurable, and the outcomes are poor. There is significant individual variation in patients with stage IVB cervical cancer, in whom standard treatment has not been well defined. This study aims to review the outcomes and discuss treatment strategies in patients with stage IVB cervical cancer. METHODS: From January 1, 1992, to December 31, 2011, we retrospectively reviewed the data of patients with stage IVB cervical cancer who were given a diagnosis at the Department of Gynecology of the Cancer Institute Hospital. RESULTS: A total of 111 patients were enrolled. At the time of analysis, the median overall survival (OS) was 16.6 months (range, 0.2-120.9 months), and the 5-year OS rate was 20.2%. The 5-year OS rate was 59.4% for those with only para-aortic lymph node metastases; 24.8% for those with lymphogenous metastases, excluding those with only para-aortic lymph node metastases; 6.1% for those with hematogenous metastases; and 0% for those with disseminated metastases. The OS in patients with lymphogenous metastases was better compared with that of those with either hematogenous or disseminated metastases (P < 0.0001). In multivariate analysis, the performance status, site of metastases (only lymph node or other metastases), and local stage were all independent prognostic factors. CONCLUSIONS: We determined performance status, site of metastases (only lymph node or other metastases), and local stage as independent prognostic factors in patients with stage IVB cervical cancer. Regarding treatment, we confirmed that the effectiveness of chemotherapy was also of significance.

Huge polypoid endometriosis: report of a case and review of the literature.

'Polypoid endometriosis' is a rare variant of endometriosis. We describe a case of an extremely large polypoid endometriosis mimicking a malignant tumor. A 37-year-old nulliparous woman was referred due to the rapid growth of an endometriotic cyst of the ovary and a high serum CA125 level. MRI revealed solid components in the pelvic mass. These preoperative clinical data were compatible with an ovarian carcinoma. A frozen section of the tumor biopsy showed as if an adenosarcoma, but finally the diagnosis of polypoid endometriosis with decidual change was made on permanent section. Polypoid endometriosis is a part of the differential diagnosis for malignant tumors in women with endometriosis, and we should consider carefully decision making for treatment.

Vulvar Reconstruction Following Surgery for Vulvar Cancer Using a Stepladder V-Y Advancement Medial Thigh Flap.

OBJECTIVE: The aim of this study was to identify the risks and benefits of the stepladder V-Y advancement medial thigh flap for vulvovaginal reconstruction in comparison to direct skin closure. METHODS: Fifty-four patients with vulvar cancer treated in our hospital between 1992 and 2013 were enrolled in this study. The cohort group (group A) consisted of 25 patients who underwent surgery from August 2006 until April 2013. During this period, we changed our surgical paradigm to incorporate reconstructive plastic surgery immediately following surgery for vulvar cancer performed by gynecologic oncologists. The control group (group B) consisted of 29 patients treated between 1992 and August 2006. During this period, our surgical approach was limited to direct skin closure with no reconstructive plastic surgery. Perioperative findings and clinical outcomes were compared retrospectively. RESULTS: Patient characteristics and surgical procedures, other than the reconstructive surgery, were the same for the 2 groups. The mean blood loss and operative times were similar, and there were no major complications in either group; however, the average length of hospital stay was significantly shorter in group A (P = 0.04). CONCLUSIONS: Stepladder V-Y advancement medial thigh flap lowers posttreatment morbidity and improves quality of life for patients with vulvar cancer. Rapid recovery from surgery is reflected in the short hospital stay, and it enables immediate induction of adjuvant therapy. It may possibly contribute to improved treatment outcome.

Secondary debulking surgery for isolated para-aortic nodal recurrence in ovarian cancer involving the division of the left renal vein.

OBJECTIVE: To present a case that involved para-aortic lymphadenectomy in the aortocaval and retrocaval region involving the division of the left renal vein (LRV). METHODS: A 36-year-old woman presented with ovarian cancer and isolated nodal recurrence located in the aortocaval and retrocaval region above and below the renal vein. Cytoreduction of para-aortic lymph nodes involving the division of the LRV was performed. RESULTS AND CONCLUSION: Division of the LRV facilitates the separation of the lymph nodes from the renal artery or inferior vena cava under direct vision. No intra- or early postoperative complications, including renal dysfunction, occurred. Further analyses with long-term follow-up are warranted to evaluate this surgical method.

Prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy followed by platinum-based chemotherapy.

OBJECTIVE: The purpose of this study was to analyze the prognosis for endometrial cancer patients treated with systematic pelvic and para-aortic lymphadenectomy (PLA and PALA) followed by platinum-based chemotherapy. MATERIALS AND METHODS: From 1994 to 2004, in the Cancer Institute Hospital, 502 patients who were surgically treated with systematic PLA and PALA were enrolled in this study. Their prognosis and clinicopathological features were retrospectively reviewed. RESULTS: One hundred ninety-one (38.0%) patients received adjuvant platinum-based chemotherapy. Lymph node (LN) metastasis was observed in 80 (15.9%) patients, pelvic-only LN metastasis in 27 (5.4%), para-aortic-only LN metastasis in 15 (3.0%), and both pelvic and para-aortic LN metastasis in 38 (7.6%). The median number of metastatic LNs was 2 (range, 1-57), 1 (range, 1-4), and 6 (range, 2-50) in patients with pelvic-only, para-aortic-only, and both pelvic and para-aortic LN metastasis, respectively (P < 0.001). Only 2.6% (2/76) of patients with no myometrial invasion had LN metastasis, and no less than 8.9% (22/247) of patients with myometrial invasion (limited to the inner half) had LN metastasis. Five-year overall survival (OS) for LN metastasis-negative and -positive patients was 96.7% and 76% (P < 0.001), respectively. Five-year OS for patients with metastasis in 1 or 2 LNs was 84.8% and was significantly higher than that for patients with metastasis in 3 or more LNs (57.8%; P = 0.011). In patients with LN metastasis, 5-year OS of endometrioid adenocarcinoma and non-endometrioid adenocarcinoma cell types was 90.2% and 56.7% (P = 0.0016), respectively. CONCLUSIONS: Under the settings of thorough PLA and PALA followed by intensive platinum-based chemotherapy for endometrial cancer, metastasis in 1 or 2 LNs seems to have little effect on survival, although para-aortic LNs are involved. This therapeutic strategy could not improve the prognosis of patients with metastasis in 3 or more LNs or patients with non-endometrioid adenocarcinoma cell types along with LN involvement.

Monitoring the impact of a national HPV vaccination program in Japan (MINT Study): rationale, design and methods.

We have developed a collaborative hospital-based approach to monitoring the impact of a human papillomavirus vaccine on cervical cancer, its precursor lesions and human papillomavirus type-specific prevalence in Japan. The monitoring will be conducted for a total period of 21 years on women aged <40 who are newly diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia or adenocarcinoma in situ at 21 participating institutes. Women are monitored to determine their vaccine history and will be human papillomavirus-genotyped each year. The primary endpoint is the human papillomavirus16/human papillomavirus18-positive rate in women aged 16-25 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ. The major secondary endpoints are the number of women aged <40 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ, the human papillomavirus type-specific prevalence, and the number of deaths from invasive cervical cancer in women aged <40. Long-term surveillance for human papillomavirus-associated cervical diseases in young females is important for the development of future strategies for cervical cancer prevention in Japan.

Recurrence patterns of advanced ovarian, fallopian tube, and peritoneal cancers after complete cytoreduction during interval debulking surgery.

OBJECTIVES: Similar to primary debulking surgery, complete resection of all macroscopic diseases during interval debulking surgery (IDS) is the primary objective while using neoadjuvant chemotherapy followed by IDS for advanced ovarian, fallopian tube, and peritoneal cancers. However, most patients develop recurrent disease even after complete cytoreduction during IDS. This study aims to identify recurrence patterns of the ovarian, fallopian tube, and peritoneal cancers in patients who underwent complete cytoreduction during IDS. METHODS: We retrospectively reviewed data of patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who were treated at our hospital from January 1, 2005, to December 31, 2011. RESULTS: In this study, 105 patients underwent neoadjuvant chemotherapy followed by IDS and achieved complete cytoreduction. The median follow-up period was 42.1 months. Recurrence was documented in 70 patients (66.7%), and 35 (33.3%) showed no evidence of disease. Peritoneal dissemination was the most common recurrence (60.0%) observed. In multivariate analysis, positive peritoneal cytology (P = 0.0003) and elevated pre-IDS serum CA125 levels (P = 0.046) were independent risk factors for recurrence. CONCLUSIONS: After complete cytoreduction during IDS in patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers, positive peritoneal cytology at IDS and elevated pre-IDS CA125 levels are associated with an increased risk of cancer recurrence. Positive peritoneal cytology during IDS is a particularly strong predictive factor for poor outcomes in these patients.