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Abstract Approximately 500,000 women are diagnosed with cervical cancer annually, with high-grade cervical intraepithelial neoplasia (CIN) estimated to be 20 times higher. The diathermy ablation is an inexpensive minimally invasive surgeries for CIN. However, little is known about the treatment outcomes. A prospective clinical trial was therefore conducted to evaluate ablation outcomes based on detailed colposcopy findings, cytology, and biopsy results over a two-year period. We enrolled CIN2 (n = 32) and CIN3 (n = 7) patients. Eligibility criteria included: aged between 29 and 49 (median: 36, mean: 36.3), visible transformation zone with high-grade lesions not entirely occupying the cervix, and histologically diagnosed with CIN2 or CIN3. Cytology and HPV genotyping were performed, and colposcopic findings were evaluated. Colposcopy-guided diathermy ablation was conducted by a certified gynecologic oncologist. The incidence of recurrent or residual disease was 5.1% (2/39, 95% confidence interval: − 0.02 to 0.12). The prevalence of HPV infection at 12 months decreased after surgery, as 67.6% (23/34, 0.52–0.83) of patients were HPV-negative. No severe adverse events were reported, while there were five pregnancies with full-term deliveries. The promising outcome was possibly due to selection of rigorous surgical indication and skilled surgical techniques. The study highlights the importance of experienced and skilled colposcopists. TrialRegistry This study was registered in the clinical trial registration system of the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR ID: UMIN000024483). Open for the trial to the public through the website: 01/11/2016. First registration of the patient: 30/01/2017.

Abstract Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95% CI: 0.933–0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p

Abstract Disease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA− (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA− (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia’s disease sites.

Abstract Persistent HPV infection associated with immune modulation may result in high-grade squamous intraepithelial lesions (CIN)2/3. Currently, there is little information on the cervicovaginal microbiome, local cytokine levels and HPV infection related to CIN. Follow-up of patients after local surgery provides an opportunity to monitor changes in the cervicovaginal environment. Accordingly, we undertook this longitudinal retrospective study to determine associations between HPV genotypes, cervicovaginal microbiome and local cytokine profiles in 41 Japanese patients with CIN. Cervicovaginal microbiota were identified using universal 16S rRNA gene (rDNA) bacterial primers for the V3/4 region by PCR of genomic DNA, followed by MiSeq sequencing. We found that Atopobium vaginae was significantly decreased (p

Abstract Precision medicine based on cancer genomics is being applied in clinical practice. However, patients do not always derive benefits from genomic testing. Here, we performed targeted amplicon exome sequencing‐based panel tests, including 160 cancer‐related genes (PleSSision‐160), on 88 malignant ovarian tumors (high‐grade serous carcinoma, 27; endometrioid carcinoma, 15; clear cell carcinoma, 30; mucinous carcinoma, 6; undifferentiated carcinoma, 4; and others, 6 (immature teratoma, 1; carcinosarcoma, 3; squamous cell carcinoma, 1; and mixed, 1)), to assess treatment strategies and useful biomarkers for malignant ovarian tumors. Overall, actionable gene variants were found in 90.9%, and druggable gene variants were found in 40.9% of the cases. Actionable BRCA1 and BRCA2 variants were found in 4.5% of each of the cases. ERBB2 amplification was found in 33.3% of mucinous carcinoma cases. Druggable hypermutation/ultramutation (tumor mutation burden ≥ 10 SNVs/Mbp) was found in 7.4% of high‐grade serous carcinoma, 46.7% of endometrioid carcinoma, 10% of clear cell carcinoma, 0% of mucinous carcinoma, 25% of undifferentiated carcinoma, and 33.3% of the other cancer cases. Copy number alterations were significantly higher in high‐grade serous carcinoma (P

The role of sialic acids on MUC1 in peritoneal dissemination of ovarian cancer cells was investigated. A human ovarian carcinoma cell line, ES-2, was transfected with full-length MUC1 containing 22 or 42 tandem repeats. These transfectants were less adherent to monolayers of patient-derived mesothelial cells than ES-2/mock transfectants. When these cells were inoculated into the abdominal cavity of female nude mice, mice that had received the transfectants showed better survival. When the transfectants were mixed with sialidase and injected, the survival was poorer, whereas when they were mixed with N-acetyl-2,3-dehydro-2-deoxyneuraminic acid, a sialidase inhibitor, the survival was significantly prolonged. These behaviors, concerned with peritoneal implantation and dissemination observed in vitro and in vivo, were dependent on the expression of MUC1. Therefore, sialic acid linked to MUC1 in the form, at least in part, of sialyl-T, as shown to be recognized by monoclonal antibody MY.1E12, is responsible for the suppression of adhesion of these cells to mesothelial cells and the suppression of peritoneal implantation and dissemination.

Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies.

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented. [ABSTRACT FROM AUTHOR]

Although concurrent chemoradiotherapy (CCRT) is an effective treatment for advanced cervical cancer, its use in advanced cervical cancer with a pedunculated cervical leiomyoma remains challenging. The prognosis of recurrent cervical cancer is poor, with a low possibility of complete response (CR). In this present study, after completion of external beam radiotherapy (EBRT) and chemotherapy (weekly cisplatin), we performed the resection of a pedunculated cervical leiomyoma. No malignant cells were identified in the pathological specimen. After the myoma resection, no cervical tumor was observed on follow-up magnetic resonance imaging (MRI). High-dose-rate intracavitary brachytherapy (HDR-ICBT) was also performed. Local control of the cervical tumor was achieved after 30 months of treatment. After CCRT, rectal hemorrhage was observed but was effectively controlled via local intervention. Twenty-four months after CCRT, the patient was given salvage chemotherapy (paclitaxel plus carboplatin) due to lymph node metastasis observed at the outside range of EBRT. Thirty months after CCRT, computed tomography showed that the metastatic lymph nodes had disappeared, and the patient achieved CR. Thus, for advanced cervical cancer with a pedunculated cervical leiomyoma, CCRT could be completed following myoma resection. In addition, salvage chemotherapy for lymph node metastasis might result in CR. In this present case, a gastrointestinal adverse event was observed after radiotherapy and salvage chemotherapy with paclitaxel plus carboplatin achieved CR. [ABSTRACT FROM AUTHOR]

Objective: BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. Methods: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (gBRCAlm), germline BRCA2 mutation (gBRCAm) and germline BRCA wild-type (gBRCAwt) were found in 185, 42 and 241 OC patients, respectively. Results: The average age at diagnosis of OC in gBRCAlm and gBRCAm was 51.3 and 58.3 years, respectively, and the difference from gBRCAwt (53.8 years) was significant. The gBRCAm carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1, and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCAA2. The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. Conclusion: There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed. [ABSTRACT FROM AUTHOR]

When monitoring a moist sample using mid-infrared spectroscopy, its thickness must be <100 µm to avoid light absorption from the water. Therefore, we propose an ultrasonic-assisted mid-infrared spectroscopic imaging method that can generate a reflection plane at a depth of 100 µm from the surface of the sample by creating an ultrasonic standing wave. A frequency of 10 MHz is required to obtain an optical path length of 100 µmin biological samples. However, because biological samples generally have high compressibility, attenuation of ultrasonic waves at this frequency is significant. We use agar as a biological phantom and observe that a reflection plane is generated inside by ultrasonic standing waves using optical coherence tomography. It is found that when the sample is vibrated with an 800-kHz ultrasonic wave, a reflection plane is generated at a depth shallower than the theoretically predicted value. We believe that the reflection plane is generated by parametric standing waves, which are based on parametric effect. We detect the waveform distortion using an acoustic emission sensor and confirm the higher harmonics that generate the observed reflection plane using a fast Fourier transform. [ABSTRACT FROM AUTHOR]

Objective: Reports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1. Methods: Patients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400-600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed. Results: Complete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%). Conclusion: Repeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1. [ABSTRACT FROM AUTHOR]

Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress. These include the evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at lower levels compared with those in normal tissues, as a prognostic marker in cervical cancer; combination therapy with 5-azacytidine and cisplatin; combination treatment focusing on tumor necrosis factor-related apoptosis-inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in endometrial cancer; and use of a demethylating agent to reactivate tumor suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes using biomarkers may be used for histological classification, evaluation of disease progression and identification of compounds that are able to modulate epigenetic changes and may be useful for uterine cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Sentinel nodes (SNs) have been observed in several reports from Japan and overseas in cases with endometrial cancer; however, no consensus has been reached regarding the types of tracers or the method of their injection. A combination of the radioisotope (RI) and dye method is considered to be desirable. We assessed SN mapping using either dye or near-infrared fluorescence imaging to clarify a suitable method in cases of endometrial cancer. Methods: Patients were enrolled from 92 patients diagnosed with endometrial cancer and having no extrauterine metastasis by the preoperative imaging between 2009 and 2014 at our institution. To identify the SNs, we performed 3 methods using either dye or fluorescence solutions in conjunction with a RI method. In the dye method, we injected indocyanine green in the uterine subserosa, visually identifying SNs as stained green. In the fluorescence method, a dilute indocyanine green solution (0.5 mg, fluorescence A or 0.25 mg, fluorescence B, each per 10 mL of solvent) was injected and the SN identified by the HyperEye Medical System. Results: The SN detection rates were 100%, 100%, and 96% using dye and fluorescence A or B solution, respectively. Pelvic SNs were detected by the 3 methods in 98%, 100%, and 96% of cases and para-aortic SNs in 65%, 88%, and 74%, respectively. Fluorescence A solution was somewhat better than dye in detecting para-aortic SNs, although not significantly so (P = 0.07). The sensitivity and negative predictive values for detecting SNs with metastases with the dye method were 92% and 98% compared with 100% and 100%, respectively, for both fluorescence solutions. Conclusions: Although both dye and fluorescence methods performed well, no method perfectly identified para-aortic SNs. The concomitant use of the RI method is required to detect para-aortic SNs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome. [ABSTRACT FROM AUTHOR]

Ovarian cancer has a poor prognosis because early detection is difficult and recurrent ovarian cancer is usually drug-resistant. The morbidity and mortality of ovarian cancer are high worldwide and new methods of diagnosis and therapy are needed. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression that are involved in carcinogenesis, metastasis, and invasion. Thus, miRNAs are likely to be useful as diagnostic and prognostic biomarkers and for cancer therapy. Many miRNAs have altered expression in ovarian cancer compared to normal ovarian tissues and these changes may be useful for diagnosis and treatment. For example, deficiencies of enzymes including Dicer and Drosha that are required for miRNA biogenesis may be adverse prognostic factors; miRNAs such as miR-214 and miR-31, which are involved in drug resistance, and the miR-200 family, which is implicated in metastasis, may serve as biomarkers; and transfection of downregulated miRNAs and inhibition of upregulated miRNAs may be effective for treatment of ovarian cancer. Chemotherapy targeting epigenetic mechanisms associated with miRNAs may also be effective to reverse gene silencing. [ABSTRACT FROM AUTHOR]

Endometrial cancer is a common gynecological malignant tumor in Western countries and its incidence has also been on the increase in Asia. Genetic abnormalities related to onset and progression of malignancy in the endometrial membrane and signaling system have been identified and the developmental mechanism of endometrial cancer is becoming elucidated. The identification of the molecules related to these abnormalities has led to new potential treatment regimens for endometrial cancer, using molecular-targeted drugs. The current chemotherapy for endometrial cancer often causes systemic side effects that require discontinuation of the treatment. Furthermore, a treatment regimen for cancers of rare histological types has not been established. Recent studies on endometrial cancer revealed patterns of genetic disorders that differ among the histological types. Genetic and molecular information that underlie pathological changes and is associated with DNA mismatch repair genes and epigenetic regulation was also identified. Targeting of these mechanisms with molecular-targeted drugs has been performed with the aim of linking treatment to the carcinogenic mechanism at the molecular and genetic levels. However, the response rates with single-agent therapy are generally low and several problems remain unresolved. Trials of combinations of molecular-targeted drugs with currently available treatments and identification of factors determining sensitivity are required to overcome these difficulties. [ABSTRACT FROM AUTHOR]

We have prepared poly(4-tert-butylstyrene-block-4-tert-butoxystyrene), BO, having very bulky and hydrophobic substituent in both components by an anionic living polymerization. The BO films with various thicknesses were prepared by the spin-coating method from toluene solutions, and they were annealed under vacuum above the glass transition temperatures of both two components. An alternating lamellar structure oriented normal to the surface was observed at the surface of the BO film with thickness more than 150 nm, where the appearance of both B and O components were confirmed by XPS measurements. It is revealed that the ordered surface structure is caused by nanophase separation of BO clearly proved by hydrolyzed surface structures. Another aspect of this work is the structure of BO block copolymer after hydrolysis reaction. The O component can be easily converted into poly(4-hydroxystyrene) which has an ability to form a hydrogen bond. Moreover, it turns out that the control of the hydrolyzed layer thickness is possible by choosing the solvents in the reaction. This hydrophilic−hydrophobic nanopatterning is expected to be useful in a template of assembling nanoparticles and peptides. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the learning experience, in addition to its impact on outcomes, in patients with benign prostatic hyperplasia (BPH) who undergo photoselective vaporization of the prostate (PVP).Patients and MethodsThe study included 74 Japanese patients who underwent PVP. All patients were assessed for treatment efficacy in outcome variables including the International Prostate Symptom Score (IPSS), quality-of-life (QOL) score, peak urinary flow rate (Qmax), and post-void residual urine volume (PVR) at 12 months after PVP. The impact of the learning curve in terms of efficacy and morbidity following PVP were also analyzed.ResultsThere was a significant improvement in each outcome variable after surgery. The median (25 and 75) values of the improved rate (IR) at 12 months after PVP were 75 (57, 87), 67 (50, 83), 103 (50, 176), and 85 (68, 96) in IPSS, QOL score, Qmaxand PVR, respectively. The IR in each outcome variable did not significantly change as the surgeon's experience increased. The time required for tissue vaporization of the adenoma and the total applied laser energy, along with the vaporized weight, significantly increased, but the efficiency of tissue vaporization did not increase as experience increased. A significant correlation was not evident between the learning curve and the total incidence of adverse events or blood loss following PVP.ConclusionPVP is a safe and effective treatment option for patients with BPH, providing good treatment efficacy and minimal bleeding, even when the surgeon has minimal experience. [ABSTRACT FROM AUTHOR]

Purpose: Clear cell carcinoma (CCC) is a rare histologic subtype that demonstrates poor outcomes in epithelial ovarian cancer. The Japanese Gynecologic Oncology Group conducted the first randomized phase III, CCC-specific clinical trial that compared irinotecan and cisplatin (CPT-P) with paclitaxel plus carboplatin (TC) in patients with CCC., Patients and Methods: Six hundred sixty-seven patients with stage I to IV CCC of the ovary were randomly assigned to receive irinotecan 60 mg/m(2) on days 1, 8, and 15 plus cisplatin 60 mg/m(2) on day 1 (CPT-P group) every 4 weeks for six cycles or paclitaxel 175 mg/m(2) plus carboplatin area under the curve 6.0 mg/mL/min on day 1 every 3 weeks for six cycles (TC group). The primary end point was progression-free survival. Secondary end points were overall survival, overall response rate, and adverse events., Results: Six hundred nineteen patients were clinically and pathologically eligible for evaluation. With a median follow-up of 44.3 months, 2-year progression-free survival rates were 73.0% in the CPT-P group and 77.6% in TC group (hazard ratio, 1.17; 95% CI, 0.87 to 1.58; P = .85). Two-year overall survival rates were 85.5% with CPT-P and 87.4% with TC (hazard ratio, 1.13; 95% CI, 0.80 to 1.61; one-sided P = .76). Grade 3/4 anorexia, diarrhea, nausea, vomiting, and febrile neutropenia occurred more frequently with CPT-P, whereas grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy, and joint pain occurred more frequently with TC., Conclusion: No significant survival benefit was found for CPT-P. Both regimens were well tolerated, but the toxicity profiles differed significantly. Treatment with existing anticancer agents has limitations to improving the prognosis of CCC., (© 2016 by American Society of Clinical Oncology.)