International Journal of Gynecological Cancer最新文献

In the era of the serous tubal intraepithelial carcinoma hypothesis, investigation continues as to what proportions of high-grade serous tubo-ovarian carcinomas originate in the distal fallopian tube versus in the ovary. In this retrospective cohort study of 118,619 patients with high-grade serous tubo-ovarian carcinoma identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2021, a diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma occurred from 2004 to 2018 that the proportional distribution of high-grade serous fallopian tubal carcinoma increased 6.1-fold from 4.5% in 2004 to 27.6% in 2018 (p-trend < .001). This rapid diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma reached a plateau at 2018, followed by steady proportional distribution of high-grade serous fallopian tubal carcinoma among the high-grade serous tubo-ovarian carcinomas for 4 consecutive years (27.6% in 2018 to 28.0% in 2021, p-trend = .801). The average rate of tubal carcinomas during this post-plateau period was 27.7%. In conclusion, the diagnosis shift in the primary site of high-grade serous tubo-ovarian carcinoma from the ovary to the fallopian tube may have ended in the late 2010s. After the implementation of College of American Pathologists diagnosis criteria, 1 in 3 to 4 high-grade serous tubo-ovarian carcinomas were classified as of fallopian tube origin.

Circulating tumor DNA (ctDNA) is a promising non-invasive tool that has been demonstrated to be a clinically useful biomarker in several tumor types for risk stratification, prognosis, and early detection of recurrence. However, there are limited data on the clinical utility of ctDNA in endometrial cancer (EC) compared with other solid tumors. The evolution of EC management through the integration of molecular characterization into the treatment algorithm has intensified the need to develop more effective predictive biomarkers to optimize treatment and reduce clinical toxicities. Given its non-invasive nature and its ability to represent and complement tumor multiclonal spatial and temporal heterogeneity, ctDNA could act as a valid surrogate for tissue sampling. In addition to plasma ctDNA detection being associated with clinicopathologic features of tumor aggressiveness at pre-operative assessment, an association with reduced disease-free survival and overall survival has been observed in patients with detectable ctDNA. Moreover, the half-life of ctDNA is significantly shorter than CA125, and plasma levels are reported to be completely cleared from the blood within 1 week from surgical debulking. Therefore, ctDNA may serve as a dynamic biomarker for occult microscopic residual disease when assessed within the first 4 to 8 weeks after eradicative surgery. Few studies have reported high sensitivity of ctDNA in detecting disease recurrence at longitudinal follow-up, although there are limited data comparing ctDNA and traditional serum biomarkers (CA125 and HE4) in identifying recurrence. In the perspective of personalized oncology, ctDNA may potentially help improve adjuvant therapeutic management by escalating/de-escalating treatment based on ctDNA detection after surgery, during maintenance, or in the recurrent/metastatic setting, in addition to acting as a sensitive biomarker for early detection of recurrence. Several challenges hinder the use of ctDNA in EC, including the lack of standardized protocols, the low mutational burden, tumor heterogeneity, and background normal DNA, which limit assay sensitivity and specificity. In addition, the high cost of ctDNA analysis, particularly, next-generation sequencing, restricts its accessibility. Future trials should focus on cost-effective approaches to ensure sustainability and efficient resource allocation.

Objective: Although trials of neoadjuvant chemotherapy for ovarian cancer use 3 cycles, real world practice varies. We evaluated the effect of higher order cycles of chemotherapy, followed by cytoreduction surgery or no surgery on survival, tumor resectability, and post-operative morbidity.

Methods: For our international, retrospective cohort study, the inclusion criteria were women with stage III to IV ovarian cancer undergoing interval (after 3-4 cycles of chemotherapy) or delayed (≥5 cycles) cytoreduction surgery or no cytoreduction surgery with chemotherapy alone (≥5 cycles). Multivariate regression analyses were used to model the effect of impact variables on overall survival and tumor resectability.

Results: Data were collected from 2498 patients from 22 centers across 12 countries. In total, 60.2% (n = 1504) underwent interval cytoreduction surgery, 30.4% (n = 760) underwent delayed cytoreduction surgery, and 9.4% (n = 234) did not undergo surgery. In the interval, delayed, and no-surgery groups, the mean follow-up periods were 57, 69, and 39 months, respectively. Patients undergoing interval versus delayed cytoreduction were more likely to achieve no residual tumor mass (no macroscopic residual disease [R0] = 72.2%, 1072/1484; 64.6%, 490/758). Patients who underwent interval versus delayed cytoreduction surgery had a greater proportion of minor (Clavien-Dindo 1-2, 32%, 471/1473; 28%, 212/756) and major (Clavien-Dindo 3-5, 9.6%, 141/1473; 8.6%, 65/756) morbidities. Interval cytoreduction surgery was associated with statistically significant greater overall survival than delayed cytoreduction surgery (HR 0.81, p = .01). R0 at the time of delayed cytoreduction was not equivalent to R0 at the time of cytoreductive surgery. R0 in the interval setting was associated with better overall survival (HR 0.77, p = .01). Patients who did not undergo surgery had twice as poor overall survival compared with patients who underwent delayed cytoreduction surgery (HR 2.01, p < .001).

Conclusions: Women receiving >4 neoadjuvant chemotherapy cycles had poorer overall survival, despite achieving R0 at surgery. Early maximum effort cytoreduction surgery with R0 in high volume centers and appropriate surgical resources are critical for increasing overall survival.

Objective: Mucinous ovarian carcinomas account for 3% of all epithelial ovarian carcinomas and are categorized into expansile or infiltrative subtypes. Nevertheless, the prognostic impact of these subtypes in stage I disease remains unclear.

Methods: This retrospective study included patients with mucinous ovarian cancer who were referred to or treated at our institution between 1976 and 2022. Pathologic review was performed by 2 expert pathologists. Only patients with stage I disease were included in this study. Tumors were characterized as expansile or infiltrative, and oncologic features were analyzed.

Results: A total of 80 cases met the inclusion criteria, with 36 and 44 patients having expansile and infiltrative subtypes, respectively. The disease stages were as follows: expansile subtype in 14 patients, stage IC in 22 patients, infiltrative subtype stage IA in 26 patients, and stage IC in 18 patients. The characteristics of the 2 groups of patients were comparable, except for the use of lymphadenectomy (more frequent in the infiltrative subtype: 28/44 [63%] vs 8/36 [22%] in expansile disease, p < .05). After a median follow-up of 79 months (range; 27.7-119.2), 10 (12.5%) recurrences occurred (3 expansile and 7 infiltrative). A total of 2 cases of expansile recurrence with pelvic recurrence were cured after secondary surgery and chemotherapy, and 1 patient died of the disease. A total of 5 patients with infiltrative recurrence had extra-pelvic spread and died of the disease, 1 patient was still alive with progressive disease, and the last was still alive and disease-free. A total of 2 cases of recurrence were observed after conservative surgery (1 of each subtype).

Conclusions: In this series, the overall and disease-free survival rates were not significantly different between patients with expansile and infiltrative stage I mucinous ovarian carcinoma. However, the prognosis of recurrent infiltrative cases is poorer than expansile cases.

Objective: To investigate the safety of neoadjuvant chemotherapy and conization in early-stage cervical cancer with a tumor size >2 cm using a fertility-sparing approach.

Methods: The ETERNITY project is a retrospective, multi-institutional study that collected data from patients with early-stage cervical cancer undergoing fertility-sparing treatment. In the present study, we report the outcomes of stage IB2 to IB3 cervical cancer undergoing nodal assessment, neoadjuvant chemotherapy, and conization. A propensity-matching algorithm was used to compare patients who underwent upfront radical surgery.

Results: A total of 395 patients were included in the ETERNITY project. Among these, 25 underwent a fertility-sparing attempt with nodal assessment, neoadjuvant chemotherapy, and conization. The median (range) patient age was 37 (24-41) years. Four (16%) patients with positive nodes required definitive chemo-radiation. Twenty-one (84%) patients received neoadjuvant chemotherapy. Two (8%) patients with stable disease underwent radical hysterectomy, whereas the remaining 19 (76%) patients who achieved a clinical response underwent cervical conization. Three (12%) patients underwent radical hysterectomy owing to persistent positive margins, leaving 16 (64%) patients who completed the planned fertility-sparing attempt. After a median (range) follow-up of 36.2 (21.9-88) months, 3 recurrences occurred. Two patients with cervical recurrence underwent hysterectomy, while 1 patient who received definitive chemoradiotherapy owing to the presence of positive nodes developed distant recurrence. Regarding obstetric outcomes, 6 patients attempted to conceive, and 4 (66.7%) pregnancies were achieved (1 was achieved with assisted reproductive technology). In a propensity-matched group of patients who underwent upfront radical surgery, no differences in morbidity or survival rates were recorded.

Conclusions: Neoadjuvant chemotherapy followed by conization should be investigated in selected patients with cervical cancer who wish to preserve their childbearing potential. Further prospective studies are needed to assess the long-term safety and identify predictors of response.

Clinical trial identifier: NCT06351228.

Background: The standard treatment for endometrial cancer is hysterectomy with or without bilateral salpingo-oophorectomy; however, this may not be an optimal choice for women who have not completed childbearing or who are at a high risk of surgical complications. Conservative treatment with levonorgestrel intrauterine devices appear to be effective in patients with early-stage endometrial cancer; however, patients with mismatch repair-deficient (dMMR) tumors have a low likelihood of responding to levonorgestrel intrauterine devices.

Primary objective: To assess the efficacy of dostarlimab, an active immune checkpoint inhibitor that targets the programmed cell death protein-1 receptor, in patients with early-stage dMMR endometrioid endometrial adenocarcinoma.

Study hypothesis: Administration of 4 3-weekly cycles of 500 mg dostarlimab followed by a 3-week rest period and 3 6-weekly cycles of 1000 mg dostarlimab will be safe and efficacious in early-stage dMMR endometrial cancer patients.

Trial design: Non-randomized, open-label, pilot, multicenter phase2b study designed to evaluate the efficacy and safety of dostarlimab in 10 women aged ≥18 years with a clinically confirmed diagnosis of early-stage and dMMR endometrioid endometrial adenocarcinoma.

Major inclusion/exclusion criteria: Eligible patients must have histologically proven stage I, International Federation of Gynecology and Obstetrics grade 1 or 2 dMMR endometrioid endometrial adenocarcinoma and desire for fertility preservation. Exclusions include, but are not limited to, patients with other high-risk endometrial cancer cell types, a poor medical risk due to uncontrolled medical conditions, or those who experienced grade 3 or higher immune-related adverse events from prior immunotherapy.

Primary endpoint(s): The primary endpoint is the number of participants achieving investigator-assessed pathological complete response within 6 months of treatment.

Sample size: Ten (10) women ≥18 years of age will be enrolled.

Estimated dates for completing accrual and presenting results: Accruals are expected to be completed by 2027, with the presentation of results by 2029.

Trial registration: NCT06278857.

Objective: This study aimed to identify factors influencing the decision to perform diverting ileostomy during cytoreductive surgery with colon resection for advanced ovarian cancer and investigate the associated complications and survival outcomes.

Methods: This was a retrospective cohort study of patients with advanced ovarian cancer who underwent cytoreductive surgery with colon resection and re-anastomosis between January 2010 and July 2020. Multivariate analysis was performed on the factors contributing to diverting ileostomy identified in the univariate analysis.

Results: Of the 134 patients, 60 (44.8%) underwent diverting ileostomies. The median follow-up was 35.75 months (range; 0.03-145.05) and the median age was 57 (range; 26-86). The anastomotic leakage rate was 3.7% (n = 5). On the univariate analysis, longer operative time (10 vs 6.4 hours), multiple bowel resections (>1 vs 1 hour), total colon resection length, pre-operative paracentesis, intraoperative ascites, and transfusion were associated with diverting ileostomy. In the multivariate analysis, longer operative time (OR 1.61, p < .0001) and total colon resection length (OR 1.06, p = .027) remained significant. Diverting ileostomy was associated with higher rates of intensive care unit admission (14.3% vs 2.8%, p = .001), dehydration (40% vs 9.5%, p < .0001), and acute kidney injury (16.4% vs 1.4%, p = .002). The median progression-free survival was similar (23.87 vs 21.24 months in non-diverted vs diverted ileostomy, p = .82).

Conclusions: Longer operative time and total length of colon resection influenced the selection of diverting ileostomy. The patients selected for diversion underwent multiple bowel resections more frequently, received more transfusions, and developed intraoperative ascites. These findings suggest that surgeons favor diversion for more extensive procedures. Patients who underwent diverted ileostomy experienced more short-term complications, likely reflecting the surgical complexity. Progression-free survival remained similar between the 2 groups, with diverse patients experiencing stoma-related morbidity over time, mainly dehydration and acute kidney injury. A prospective model to predict anastomotic leak risk may reduce diverting ileostomy rates.

Objective: Oral contraceptives reduce ovarian cancer risk, but the mechanism of risk reduction is not understood. We examined whether oral contraceptive pill (OCP) use influences p53 signatures, which are putative early fallopian tube precursors for high-grade serous ovarian carcinomas.

Methods: For this retrospective cohort (n = 250) of subjects aged over 50 years who had fallopian tubes removed at the time of a benign gynecologic procedure, we used health records to identify 72 patients who used OCPs for at least 5 years and 178 subjects with no history of OCP use. Immunohistochemistry for p53 was performed on all fallopian tube sections, with 8 individuals removed for lack of identifiable tissue. p53 Signatures were identified and stratified based on size. Logistic regressions were run to estimate the association between OCP use and p53 lesion and lesion size.

Results: There was no difference in the occurrence of p53 lesions with 20 of 70 of OCP users (28.6%) and 57 of 172 of those with no history of OCP use (33.1%). Subjects who used OCPs were more likely to have a small lesion (OR 1.98, 95% CI 1.03 to 3.83) and had decreased risk of having a medium/large lesion (OR 0.38, 95% CI 0.18 to 0.79). A total of 2 serous tubal intraepithelial lesions and 2 serous tubal intraepithelial carcinomas were identified in OCP-naive patients, whereas none were found in those with a history of OCP use.

Conclusions: OCP exposure was associated with a shift toward smaller p53 lesion size but was not found to be associated with a difference in the number of p53 lesions between OCP-exposed and unexposed patients. Future research should examine whether OCP use reduces proliferation and clonal expansion of p53 signature lesions toward higher risk precursors and, eventually, cancer. There were no serous tubal intraepithelial lesions and serous tubal intraepithelial carcinomas in patients with OCP exposure.

Neuroendocrine cervical carcinomas are rare, aggressive tumors with a high risk of early metastasis and poor survival outcomes. Despite existing therapies, over half of patients experience recurrence or progression after primary treatment, and survival after recurrence remains limited. Survival rates have not significantly improved over the past several decades, underscoring an urgent need for better therapeutic options. The rarity of neuroendocrine cervical carcinoma has precluded randomized trials, leaving treatment strategies to be guided by small retrospective studies or adapted from protocols for small cell lung cancer. However, as we gain a deeper understanding of its unique origin, genomic landscape, and biological characteristics, it has become clear that neuroendocrine cervical carcinoma requires distinct management strategies. Key questions in managing neuroendocrine cervical carcinoma remain unanswered: does adjuvant radiation therapy improve outcomes for early-stage disease? Should neoadjuvant chemotherapy be considered for patients with bulky, localized tumors? Can immunotherapy improve outcomes when added to chemoradiation in locally advanced cases? Should immunotherapy be a standard option for recurrent disease? Addressing these questions requires a thorough understanding of the unique molecular and biological characteristics of neuroendocrine cervical carcinoma and its clinical behavior. This review aims to provide an updated summary of the molecular landscape of neuroendocrine cervical carcinoma, highlighting features that distinguish it from small cell lung cancer and align with other types of cervical cancer. We discuss current treatment approaches, identify gaps in knowledge, and examine paradigm-shifting clinical trials that have significantly impacted survival outcomes in cervical cancer and small cell lung cancer, translating these insights into potential strategies for neuroendocrine cervical carcinoma. By focusing on the unique aspects of neuroendocrine cervical carcinoma, this review emphasizes the need for specialized treatment strategies for this challenging disease.