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 platinum re-challenge is a treatment option for patients with advanced/recurrent endometrial cancer, real-world outcomes for these patients in Europe are not well-documented. Thus, this study aimed to evaluate real-world treatment patterns and outcomes for platinum re-challenge in patients with advanced/recurrent endometrial cancer.

Methods: Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a multi-center, retrospective, medical record review conducted in France, Germany, Italy, Spain, and the United Kingdom, evaluating treatment patterns and outcomes. Patients with advanced/recurrent endometrial cancer treated with first-line systemic therapy and experiencing disease progression between July 2016 and June 2019 were eligible for inclusion in ECHO-EU. This analysis used data from a subset of patients, the platinum re-challenge cohort, who received platinum-based chemotherapy as second-line therapy after previous adjuvant/neoadjuvant and/or first-line platinum therapy. Kaplan-Meier analyses since initiation of second-line therapy estimated real-world progression-free survival and overall survival.

Results: Of the 475 ECHO-EU patients, 70 patients (15%) were platinum re-challenged and had a median age of 67 years (range; 44-81). The platinum-free interval (PFI) was <6 months for 27 patients (38.6%) and >6 months for 43 patients (61.4%). Complete or partial response to second-line therapy were achieved in 37.1% of patients, with similar overall response rates reported for patients with PFI <6 months (33.3%) and PFI ≥6 months (39.5%). The median (95% CI) overall survival from second-line therapy was 12 months (11-not estimable [NE]) overall and 14.1 (8.7-NE) and 12.0 (10.5-NE) months for patients with PFI <6 months and PFI >6 months, respectively. The median real-world progression-free survival from initiation of second-line therapy was 8.1 months (95% CI 7.6 to 10.0) overall and 7.6 (95% CI 5.3 to 19.8) and 8.5 (95% CI 7.9 to 12.0) months for patients with PFI <6 months and PFI ≥6 months, respectively.

Conclusion: Patients with advanced/recurrent endometrial cancer who were re-challenged with a platinum-based therapy had similar outcomes, irrespective of their PFI, indicating that further research is needed to assess the value of PFI in endometrial cancer. The findings also suggest an unmet medical need and scope for novel treatments that may improve the overall survival for these patients.

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: Lymphovascular invasion can predict nodal spread and recurrence in endometrioid endometrial cancer; however, the impact of lymphovascular invasion quantification on local versus distant recurrence in surgically staged patients has not yet been established.

Methods: This multicenter, retrospective cohort study included surgically staged patients with International Federation of Obstetrics and Gynecology 2009 stage I node-negative endometrioid endometrial cancer. Patients were treated between January 2012 and December 2019 at 2 tertiary cancer centers. Staging included a total hysterectomy and lymph node assessment. The extent of lymphovascular invasion was defined using the World Health Organization criteria as focal (<5 vessels involved on at least 1 pathology slide) or substantial (≥5 vessels involved). Recurrence and death were considered as events. A competing risk analysis was performed and controlled for multicenter clustering.

Results: Overall, 1555 patients met the inclusion criteria: 65 (4.2%) had substantial invasion, 119 (7.7%) had focal, and 1371 (88.2%) had no invasion. The median follow-up was 61.5 months (range; 0.8-133.9). There were 173 evaluable events among the 1554 patients: 56 local recurrences, 43 distant recurrences, and 74 deaths without recurrence. Deep (>50%) myoinvasion and grade 3 histology were more frequently observed in patients with substantial myoinvasion. Overall, 323 patients (20.8%) received adjuvant therapy. The 5-year cumulative incidence failure rates for any recurrence were 6.0% for no, 19.5% for focal, and 19.0% for substantial invasion. Compared to no lymphovascular invasion, substantial invasion was associated with an increased risk of distant recurrence (adjusted HR 2.29, 95% CI 1.17 to 4.46).

Conclusions: In patients with surgical stage I endometrioid endometrial cancer, the focal and substantial lymphovascular invasion was associated with a 3-fold increased risk of cumulative incidence failure versus no lymphovascular invasion. Patients with substantial invasion had more deeply invasive and grade 3 tumors and appeared to experience more distant than local recurrences. These findings challenge the International Federation of Obstetrics and Gynecology 2023 staging classification that combines no lymphovascular invasion and focal lymphovascular invasion into a single risk category.

This retrospective study aimed to analyze the fertility results and oncologic outcomes of patients with stage II and III serous borderline ovarian tumors after fertility-sparing surgery and to seek future fertility. Among 224 patients with stage II and III serous borderline ovarian tumors treated or referred to our institution, 74 (33%) underwent fertility-sparing surgery. Median time of follow-up was 4.1 years (range; 3.2-7.9); 35 (47%) patients attempted to be pregnant and 21 (60%) had at least 1 pregnancy. Nineteen live-birth pregnancies were observed (9 spontaneously) in 18 patients (all but 1 with non-invasive implants). Seven patients had recurrent disease treated conservatively before pregnancy and 8 recurred after pregnancy (6 recurred as ovarian borderline tumors and 1 as a low-grade serous carcinoma).