OBJECTIVE:The standard surgery for stage IB uterine cervical cancer is radical hysterectomy (RH). However, RH is highly invasive, and there is a need to establish less invasive techniques. METHODS:We conducted a prospective, single-arm trial to evaluate the efficacy and safety of modified radical hysterectomy (MRH)in patients with International Federation of Gynecology and Obstetrics 2008 stage IB1 cervical cancer involving a tumor diameter of ≤2 cm measured on magnetic resonance imaging. The protocol treatment consisted of MRH and adjuvant (chemo)radiotherapy if indicated. The primary endpoint was 5-year overall survival (OS). The expected OS was set at 95.8%; i.e., the OS of RH in our previous observational study. RESULTS:Of 225 eligible patients, 193 (85.8%) had pT1b1 (Union for International Cancer Control 7th) disease, and 184 (81.8%) had a pathological maximum tumor diameter of ≤2 cm. Parametrial involvement, lymph node metastasis, stromal invasion involving ≥2/3 of the stroma, and surgical margins of <1 cm (including carcinoma in situ) were observed in 3 (1.3%), 16 (7.1%), 30 (13.3%), and 11 (4.9%) patients, respectively. The 5-year OS and relapse-free survival rates were 98.2% (90% confidence interval [CI]=96.0%-99.2%) and 94.7% (95% CI=90.8%-96.9%), respectively. The median time to the disappearance of residual urine after urethral catheter removal was 1 day. There were no treatment-related deaths. Grade 3/4 adverse events were observed in 17 patients (7.6%). CONCLUSION:MRH may be as effective as and less invasive than RH for stage IB1 uterine cervical cancer involving a tumor diameter of ≤2 cm. TRIAL REGISTRATION:Japan Registry of Clinical Trials Identifier: jRCTs031180167.

Abstract Background Hereditary breast and ovarian cancer (HBOC) confers a markedly increased lifetime risk of breast and ovarian cancers. As no effective surveillance method for early detection of ovarian cancer has been established, risk-reducing salpingo-oophorectomy (RRSO) is recommended for patients with HBOC to prevent disease onset. We evaluated the clinical characteristics of patients with HBOC and the surgical outcomes of RRSO performed at our institution. Methods We retrospectively reviewed women diagnosed with HBOC at our institution between 2018 and 2024. For analyses of surgical outcomes, male patients, patients with prior bilateral adnexectomy, and patients diagnosed with HBOC who did not undergo RRSO were excluded. Clinical data including patient characteristics, surgical procedures, genetic testing, and pathological findings were assessed. Results A total of 283 women were diagnosed with HBOC, and 43 (15.1%) underwent testing based on the results of affected relatives. After excluding 39 patients with prior bilateral adnexectomy, and 105 who did not undergo RRSO, 139 patients were included in the surgical analysis. The uptake rate of RRSO among female patients with HBOC was 57%. The median age at surgery was 50 years (range, 35–75). Pathogenic BRCA1 variants were identified in 48 patients (34.5%), BRCA2 variants in 90 (64.7%), and both BRCA1 and BRCA2 variants in 1 (0.7%). A history of malignancy was observed in 121 patients (breast cancer, n = 121; pancreatic cancer, n = 1; ovarian cancer, n = 1; others, n = 3). Laparoscopic RRSO was performed in 138 cases, with one additional hysterectomy performed laparoscopically and one via laparotomy. No perioperative complications were observed. All 6 cases before April 2020 were performed outside insurance coverage; after insurance coverage was initiated in April 2020, 16 were non-covered and 117 were covered by insurance. Pathological examination revealed occult high-grade serous carcinoma in 4 patients (2.9%) and serous tubal intraepithelial carcinoma in 5 patients (3.6%). To date, no cases of primary peritoneal carcinoma following RRSO have been identified. Conclusions RRSO was performed safely at our institution, with the detection rate of intraepithelial and invasive carcinoma comparable to previous reports. Although no cases of primary peritoneal carcinoma have been observed postoperatively to date, the residual risk remains, indicating the need for continued long-term surveillance.

ObjectiveThe prognostic implications of surgical outcomes in older adults with ovarian cancer remain unclarified. This study aimed to describe temporal trends in surgical management and examine the association between surgical outcomes and survival among older patients with ovarian cancer.MethodsThis population-based retrospective study analyzed data from the Osaka Cancer Registry from patients diagnosed with ovarian cancer between 2004 and 2018. During this period, 10,033 women were diagnosed with malignant ovarian tumors in Osaka Prefecture, of whom 7,285 were classified as epithelial ovarian malignancies. Among them, 1,441 patients aged ≥70 years were identified. After excluding 39 patients with unknown surgical outcomes and 40 with insufficient chemotherapy data, 1,365 patients were included. Based on the surgical outcomes, patients were classified as having complete resection with no residual tumor, residual macroscopic tumor-present, or no surgery. Disease extent was categorized as localized, regional, or distant. Overall survival was assessed using univariate and multivariate models.ResultsThe proportion of patients managed without surgery increased over the study period, from 20.9% in 2004–2007 to 29.0% in 2016–2018, although this trend did not reach statistical significance (p = 0.11). This shift was most evident among patients with advanced disease (p < 0.001), indicating a temporal change in surgical management among older patients. A stepwise survival gradient was observed according to surgical outcome. The 5-year overall survival rates were 63.9%, 27.9%, and 9.9% for complete resection, residual macroscopic tumor, and no surgery, respectively. Compared with complete resection, the hazard ratios for mortality were 2.63 (95% CI, 2.22–3.10) for residual macroscopic tumor and 5.37 (95% CI, 4.55–6.34) for no surgery. In multivariate analysis, surgical outcome remained associated with overall survival after adjustment for available clinical variables.ConclusionIn this registry-based cohort of patients aged ≥70 years, the proportion of patients managed without surgery increased over time, particularly among those with advanced disease, and receipt of surgery was associated with longer overall survival. However, as comorbidity and frailty data were unavailable in the registry, residual confounding related to treatment selection cannot be excluded.

BACKGROUND:Comprehensive genomic profiling (CGP) has been used to identify mutations in several hundred cancer-related genes. Patients may receive treatment that targets specific genetic mutations revealed by CGP. This study aimed to investigate the usefulness of CGP in gynecologic malignancies. METHODS:Hospital records including CGP and clinical information were reviewed from 20 institutions in the Kinki District of Japan for patients with gynecological malignancies who underwent CGP. RESULTS:A total of 724 patients were included, of whom 162 had cervical cancer, 157 had endometrial cancer, 327 had ovarian cancer, 29 had other cancers, and 49 had sarcomas. Actionable gene alterations were identified in 370 (51.1%). The most commonly altered genes were PIK3CA (14.4%), high loss of heterozygosity (12.4%), and high tumor mutation burden (10.9%). Matched therapy, based on actionable gene alterations, was administered to 73 patients (10.1%). Of these, 23 patients received matched therapy for a high tumor mutation burden, 10 for high microsatellite instability and BRCA1/2, six for ERBB2, and five for PIK3CA. Twenty-five patients died before receiving their CGP results. The objective response and disease control rates were 23.6% and 41.8%, respectively. Of the 122 patients to whom genetic counseling was recommended, 68 accepted. CONCLUSIONS:CGP testing for gynecological malignancies in Japan may improve therapeutic efficacy. However, several issues remain to be addressed, including the low matched therapy rate and death prior to availability of CGP test results.

OBJECTIVE:Tisotumab vedotin resulted in significantly longer overall survival compared with chemotherapy as second- or third-line therapy for recurrent or metastatic cervical cancer in the phase III, multi-national, open-label innovaTV 301/ENGOT-cx12/GOG-3057 trial. We report the results of a sub-group analysis of enrolled Japanese patients. METHODS:Patients were randomized 1:1 to tisotumab vedotin or investigator-choice chemotherapy (topotecan [nogitecan hydrochloride], vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. RESULTS:Among 502 randomized patients, 101 were Japanese (tisotumab vedotin, n = 50; chemotherapy, n = 51). With 13.7 months of median follow-up in Japanese patients, median overall survival was 15.0 months (95% confidence interval [CI] 9.7 to not estimable) with tisotumab vedotin and 8.5 months (95% CI 6.8 to 10.6) with chemotherapy, representing a 55% lower risk of death with tisotumab vedotin than chemotherapy (hazard ratio 0.45, 95% CI 0.27 to 0.77). Median progression-free survival was 4.0 months (95% CI 3.0 to 4.4) with tisotumab vedotin and 2.0 months (95% CI 1.5 to 3.0) with chemotherapy (hazard ratio 0.63, 95% CI 0.42 to 0.95). The confirmed objective response rate was 24.0% (95% CI 13.1 to 38.2) with tisotumab vedotin and 2.0% (95% CI 0.0 to 10.4) with chemotherapy. All patients in the tisotumab vedotin and chemotherapy arms had ≥1 treatment-emergent adverse event; grade ≥3 events occurred in 42.9% and 66.0%, respectively. Six patients (12.2%) discontinued tisotumab vedotin due to treatment-emergent adverse events. CONCLUSIONS:Consistent with global findings, tisotumab vedotin resulted in clinical improvement compared with chemotherapy across all efficacy end points, and demonstrated a manageable adverse event profile in Japanese patients with recurrent or metastatic cervical cancer.

OBJECTIVE:DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. METHODS:Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigator-assessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. RESULTS:In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32-1.12) and durvalumab + olaparib (0.44, 95% CI=0.22-0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. CONCLUSION:Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.

5512 Background: DUO-E (NCT04269200) showed statistically significant and clinically meaningful progression-free survival (PFS) with carboplatin/paclitaxel (CP) plus durvalumab (D) followed by D (CP+D) ± maintenance olaparib (O) vs CP in endometrial cancer (intent-to-treat [ITT] population; primary endpoints). The greatest benefit for CP+D was in mismatch repair deficient (dMMR) patients (pts); addition of O (CP+D+O) further enhanced PFS in MMR proficient (pMMR) pts (prespecified exploratory analyses). We present exploratory longitudinal circulating tumor (ct)DNA analyses. Methods: Pts were randomized 1:1:1 to CP (CP alone), CP+D, or CP+D+O arms. ctDNA was analyzed in plasma at baseline (BL; Cycle 1 Day 1 [C1D1]), during the chemotherapy phase (C3D1), prior to maintenance initiation (C7D1), and during the maintenance phase (C9D1) using the methylation-based Guardant Infinity assay (Guardant Health, Palo Alto, CA). Results: Of 718 pts randomized, the biomarker-evaluable population (BEP) comprised 347, 349, 350, and 349 pts at BL, C3D1, C7D1, and C9D1, respectively. Pt characteristics were similar to the ITT population but fewer pts had Eastern Cooperative Oncology Group status 1. ctDNA was detectable in 80% (278/347) of C1D1 samples, and presence of BL ctDNA was associated with shorter PFS across treatment arms. In both dMMR and pMMR pts, CP+D treatment during the chemotherapy phase led to numerically greater reductions in detectable ctDNA vs CP at C3D1; continued treatment with D led to lower ctDNA detection at C9D1 (Table) due to a lower proportion of pts switching from no detectable ctDNA to detectable (re-emergence) ctDNA between C7D1 and C9D1. The addition of maintenance O to CP+D had limited effect on ctDNA levels in dMMR pts; however, in pMMR pts, the ctDNA detection rate was lower at C9D1 vs CP or CP+D due to increased ctDNA clearance from C7D1 to C9D1 (CP+D+O vs CP+D: 48% vs 17%). Conclusions: In this post hoc exploratory analysis, BL ctDNA was associated with shorter PFS. The addition of D was associated with rapid reductions in ctDNA detection during chemotherapy and less re-emergence of ctDNA during maintenance. The addition of maintenance O was associated with further reduction of detectable ctDNA and increased ctDNA clearance in pMMR pts, reflecting an additional activity of the combination. Clinical trial information: NCT04269200 . ctDNA detection rates (% [n/N]). Population Treatment arm C1D1 C3D1 C7D1 C9D1 BEP CP 80 (94/118) 44 (51/117) 35 (41/117) 50 (58/117) CP+D 86 (96/112) 26 (29/112) 27 (30/112) 33 (37/112) CP+D+O 75 (88/117) 31 (37/120) 21 (26/121) 25 (30/120) dMMR CP 79 (11/14) 57 (8/14) 21 (3/14) 43 (6/14) CP+D 91 (21/23) 23 (5/22) 32 (7/22) 22 (5/23) CP+D+O 85 (22/26) 41 (11/27) 18 (5/28) 22 (6/27) pMMR CP 80 (83/104) 42 (43/103) 37 (38/103) 50 (52/103) CP+D 84 (75/89) 27 (24/90) 26 (23/90) 36 (32/89) CP+D+O 73 (66/91) 28 (26/93) 23 (21/93) 26 (24/93)

We investigated clinical implications of CRP and its receptor, LOX-1, in cervical cancer progression and the underlying mechanisms. Clinical data from 121 patients with cervical cancer administered definitive radiotherapy were analyzed to investigate the relationship among pretreatment serum CRP levels, tumor LOX-1 expression, and treatment outcomes. Clinical samples, cervical cancer cell lines, and mouse xenograft models of cervical cancer were employed to elucidate the mechanisms for CRP-mediated progression of cervical cancer, focusing on LOX-1 expression on cancer and myeloid-derived suppressor (MDSCs) cells. Patients with elevated pretreatment CRP levels showed significantly shorter overall survival when their cervical tumor expressed LOX-1. In contrast, elevated pretreatment CRP levels had no prognostic relevance in patients with cervical tumors not expressing LOX-1. CRP treatment of LOX1-expressing cervical cancer cells induced ERK phosphorylation and stimulated cell proliferation in vitro. In vivo, CRP treatment promoted the progression of LOX-1-expressing cervical cancer. In vitro, it stimulated MDSC survival and augmented their suppressive activity. However, the tumor-promoting effects of CRP were minimal in tumors not expressing LOX-1. In conclusion, CRP facilitates progression of LOX-1-expressing cervical cancer by stimulating LOX-1 and its downstream effectors in cancer cells and MDSCs. Novel treatments targeting CRP or LOX-1 may be against LOX1-expressing cancer.

Aim: To compare the surgical and oncologic outcomes between patients with locally recurrent cervical cancer undergoing robotic-assisted salvage radical hysterectomy (RH) and those undergoing conventional open salvage RH, performed by a single surgeon. Methods: This retrospective comparative observational study utilized data obtained from consecutive patients with locally recurrent cervical cancer, developed after definitive radiotherapy. These patients either underwent robot-assisted RH (robotic group) or conventional open RH (open group). Clinicopathological characteristics, surgical outcomes, and oncological outcomes were compared between the two groups. Results: The operative time was slightly longer in the robotic group; however, this difference was not statistically significant. Estimated blood loss was significantly lower in the robotic group (median; 0 mL [robotic group] vs. 700 mL [open group]: p < 0.01). The incidence of intraoperative and early and late complications did not statistically differ between the two groups. The mean follow-up was 29.0 and 17.1 months in the open and robotic groups, respectively. Disease recurrence rates were similar between the two groups (40% [robotic group] vs. 44.4% [open group]). Kaplan-Meier survival analysis for progression-free survival and overall survival did not show statistically significant differences between the two groups. Conclusion: Robot-assisted salvage RH in women with locally recurrent cervical cancer showed perioperative and oncological outcomes comparable to those of the open procedure. Although our results suggest that the robot-assisted approach is as good as or better than the open approach, further investigation is required to establish a more robust conclusion.

Small -cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. This study established a panel of organoid lines from patients with SCNEC of the cervix and ultimately focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. Tracking single cells indicated the existence of cells with bipotential differentiation toward SCNEC and adenocarcinomas. Single -cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for keratin 19 expression, changes in the differentiation of each cell were shown to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state. (Am J Pathol 2024, 194: 415-429; https://doi.org/ 10.1016/j.ajpath.2023.11.013)

Seromucinous borderline tumors (SMBT) are papillary neoplasms without invasive capabilities. Originally categorized as ovarian tumors, SMBT, being an endometriosis-related tumor, can manifest beyond the ovaries. To date, only four cases of extraovarian SMBT have been documented in literature. In this report, we present our experience with the first case of SMBT in the uterine cervix, which exhibited highly elevated CA19-9 levels. The patient, initially clinically diagnosed with cervical cancer, underwent treatment with radical hysterectomy and was later pathologically diagnosed with SMBT of the uterine cervix. While extraovarian SMBT, especially in the uterine cervix, is extremely rare, this condition should be considered in patients with cervical masses lacking pathological evidence of malignant disease but displaying elevated CA19-9 levels.

We aimed to investigate the trends in the incidence and treatment of endometrial cancer (EC) during potentially reproductive age in Japan, with a special focus on the relative oncologic safety of hormonal therapy (HT) over surgery. This population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry from 2004 to 2018. Women with EC were first identified and then distributions of age, stage, histology, and initial treatment were examined. Then, the relative oncologic safety of HT over surgery in patients under the age of 50 years was evaluated. Among the 9417 patients with EC, 1937 were diagnosed during their potentially reproductive age (< 50 years). The incidence of EC during potentially reproductive age has increased from 18.5

OBJECTIVE:To examine the association between adjuvant chemotherapy and survival outcomes in patients with stage I uterine leiomyosarcoma (uLMS). METHODS:This comprehensive systematic review and meta-analysis through December 31, 2023 (PROSPERO registration number: CRD42024504776) investigated studies that examined survival outcomes in patients with stage I uLMS using 4 public search engines (PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials). Two investigators searched the studies independently, and survival outcomes (overall survival [OS] and disease-free survival [DFS]) were compared between the adjuvant chemotherapy and observation groups. Utilization rate of adjuvant chemotherapy and the regimens used were also assessed. Kaplan-Meier survival curves in the two treatment groups were evaluated using ImageJ software. RESULTS:From 1988 to 2022, 16 eligible studies including a total of 5690 patients met the inclusion criteria and evaluated the effect of adjuvant chemotherapy on survival outcomes in patients with stage I uLMS. Adjuvant chemotherapy was utilized in 38.5 % of patients (range, 14.8 % to 70.0 %). Eight studies from 2017 to 2022 compared the survival outcomes between adjuvant chemotherapy and observation. OS was comparable between the two groups in both unadjusted (n = 6, hazard ratio [HR] 1.02, 95 % confidence interval [CI] 0.77-1.35, P = 0.88) and adjusted (n = 4, HR 0.90, 95 %CI 0.56-1.43, P = 0.65) pooled analyses. DFS was also similar between adjuvant chemotherapy and observation in both unadjusted (n = 4, HR 0.78, 95 %CI 0.53-1.13, P = 0.18) and adjusted (n = 2, HR 1.14, 95 %CI 0.67-1.94, P = 0.64) pooled analyses. Adjuvant chemotherapy regimens utilized included doxorubicin, ifosfamide, cisplatin, gemcitabine, and docetaxel as monotherapies or combination therapies. CONCLUSIONS:In this contemporaneous systematic review and meta-analysis, less than 40 % of patients received adjuvant chemotherapy for stage I uLMS and adjuvant chemotherapy which was not associated with improved survival. These results support the current National Comprehensive Cancer Network clinical practice guidelines that recommends de-escalating adjuvant chemotherapy in stage I uLMS after complete resection.

OBJECTIVE This study aimed to investigate the prognostic significance of tumor size and number of positive pelvic lymph nodes (PLN) in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC1 cervical cancer patients. METHODS Clinical data from 626 women with cervical cancer treated at Osaka International Cancer Center in 2010-2020 were retrospectively reviewed. Using the cutoff value obtained on the receiver operating characteristic analysis, the prognostic significance of tumor size and number of positive PLN in stage IIIC1 patients was first evaluated via uni- and multivariate analyses. Then, the impact of incorporating tumor size and number of positive PLN into the FIGO staging system was investigated using the Kaplan-Meier method. RESULTS Among 196 women with Stage IIIC1 disease, larger tumors (>4 cm) and multiple PLN metastases (≥4) were independent predictors of progression-free survival (PFS) in patients with stage IIIC1 cervical cancer. The PFS of patients with stage IIIC1 disease was inversely associated with the number of risk factors. Although patients with stage IIIC1 disease had significantly increased survival rates compared to those with stage IIIA or IIIB disease in the original FIGO 2018 staging system, this reversal phenomenon was resolved by incorporating larger tumors (>4 cm) and multiple PLN metastases (≥4) into the revised staging system. CONCLUSIONS Incorporating tumor size and number of metastatic lymph nodes into the FIGO staging system allows additional risk stratification for women with stage IIIC1 cervical cancer and improves survival prediction performance.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

LEN+PEM is an effective treatment option for advanced endometrial cancer (EC), however the prior clinical trial enrolled only a limited number of Japanese patients (pts), and further evaluation of efficacy and safety in Japanese pts is warranted. This is the first multicenter, retrospective and prospective cohort study with the largest sample size of LEN+PEM for EC in Japan, with a planned enrollment of 100 pts. We performed an interim analysis when 56 pts were enrolled. Pts with EC who had progressed after at least one platinum-containing chemotherapy and received LEN+PEM after January 2022 were enrolled. The primary endpoint was progression-free survival (PFS). The major secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Of 56 pts, mismatch repair (MMR) status of tumor was MMR-deficient in 5 (8.9%), MMR-proficient in 34 (60.7%), and unknown in 17 (30.4%). 24 pts (42.9%) had one prior chemotherapy regimen and 32 pts (57.1%) had ≥2 regimens before LEN+PEM. At data cutoff (May 31, 2023), median follow-up period was 184.5 days. Median PFS was 224 days (95% confidence interval [CI]: 108-280) and median OS was 371 days (95% CI: 254-not reached). ORR was 32.6% (95% CI: 20.9-47.0) and DCR was 78.3% (95% CI: 64.4-87.7). Common adverse events (AEs) (incidence rate ≥30%) were hypertension (67.9%), hypothyroidism (64.3%), fatigue (58.9%), thrombocytopenia (53.6%), proteinuria (50.0%), decreased appetite (44.6%), hand-foot syndrome (39.3%), aspartate/alanine aminotransferase increased (30.4%/35.7%), and diarrhea (32.1%). AEs of grade ≥3 (incidence rate ≥10%) were hypertension (21.4%), hand-foot syndrome (14.3%), thrombocytopenia (10.7%), proteinuria (10.7%), and fatigue (10.7%). AEs with a delay of ≥2 weeks from first onset to most severe grade onset were anemia, proteinuria, hand-foot syndrome, hypothyroidism, decreased appetite, and weight decreased. The therapeutic effect of LEN+PEM was consistent with that of the prior trial. The degree and frequency of AEs in Japanese pts tended to be higher than in the prior trial, and further research in real-world settings is warranted.

This study aimed to introduce FD-2, a newly developed anticervical stenosis device for patients with cervical cancer undergoing radical trachelectomy. Using ethylene-vinyl acetate copolymers, we developed FD-2 to prevent uterine cervical stenosis after radical trachelectomy. The tensile test and extractables and leachables testing were performed to evaluate FD-2’s safety as a medical device. FD-2 was indwelled in three patients with cervical cancer during radical trachelectomy and its utility was preliminarily evaluated. FD-2 consists of a head (fish-born-like structure), neck (connecting bridges), and body (tubular structure); the head is identical to FD-1, an intrauterine contraceptive device. FD-2 passed the tensile test and extractables and leachables testing. The average time required for the application or removal of FD-2 in cervical cancer patients was less than 10 s. The median duration of FD-2 indwelling was 8 weeks. No complications, including abdominal pain, pelvic infections, or hemorrhages, associated with FD-2 indwelling were reported. At the 3–12-month follow-up after the radical trachelectomy, no patients developed cervical stenosis or experienced dysmenorrhea. In conclusion, we developed FD-2, a novel device that can be used for preventing cervical stenosis after radical trachelectomy for uterine cervical cancer.