Introduction: Women with vulvar cancer are considerably older than those with other gynaecological malignancies, raising concerns about the tolerability of radical surgery. Yet, for locally advanced or recurrent disease, pelvic exenteration may be the only curative option. Robust evidence to guide decision-making in this population is lacking. Material and methods: This multicentre observational cohort study used data from the COREPEX registry including women who underwent anterior or total pelvic exenteration between 2005 and 2023 across 20 European tertiary referral centres. The primary outcome was overall survival (OS); secondary outcomes were progression-free survival (PFS) and major postoperative complications. Associations were assessed using multivariable Cox and binomial regression models adjusted for relevant covariates. Results: Among 861 women, 79 (9.2%) had vulvar cancer. Median follow-up was 49 months for OS and 40 months for PFS. Women with vulvar cancer were older and more often overweight. Five-year OS was 32% (95% CI, 19-46) in vulvar cancer versus 29% (95% CI, 25-34) in other cancers, adjusted HR 1.05 (95% CI, 0.75-1.46). Five-year PFS was 34% versus 29%, adjusted HR 0.96 (95% CI, 0.69-1.34). Major complications occurred in 33% vs 29%, adjusted RR 1.12 (95% CI, 0.77-1.58). Lymph node metastases, positive margins, and recurrent or persistent disease independently predicted poorer survival. Conclusion: Despite their older age, women with vulvar cancer had survival and morbidity comparable to those with other gynaecological malignancies. These findings support pelvic exenteration as a curative option for selected women with vulvar cancer when complete resection is feasible.

OBJECTIVES: LBN is a rare variant of uterine smooth muscle tumors. Although LBN is a benign variant of leiomyoma, recurrent cases have been reported. In our study, we aimed to evaluate the clinicopathological features of LBN cases and to define the characteristics of recurrent cases. MATERIAL AND METHODS: Seventy-six cases with LBN identified in the final pathology were included in the study. The patients’ physical examination findings, imaging reports, postoperative complications, and medical data related to recurrence, metastasis, disease-free survival, and overall survival after LBN diagnosis were retrospectively evaluated. An immunohistochemical evaluation of the cases was conducted. RESULTS: Average patient age: 42.3 years. Myomectomy: 46.1%; hysterectomy: 53.9%. Mean follow-up: 40.4 months. Recurrence: 2 cases (2.6%), both in the uterus and myomectomy group. Post-myomectomy pregnancies: 8 out of 35 cases (22.9%). Mitotic count: 2.7. ER positivity: 30%; PR positivity: 33.8%. Ki-67: negative in 56.6%, focal positivity in 42.1%, diffuse positivity in 1.3%. p16 positivity: 14.5%; p53 positivity: 22.4%. PHH3 distribution: various levels from 0/10 to 9/10 BBA. Both recurrences managed with myomectomy, identified as LBN recurrences. CONCLUSIONS: LBN is a rare type of uterine smooth muscle tumor with a low recurrence rate, primarily affecting women of reproductive age, making conservative treatments like myomectomy appropriate. However, concerns about morcellation remain. While immunohistochemistry markers and the mitotic index help differentiate between LBN and LMS, their effectiveness in predicting recurrence and prognosis in LBN is limited.

This comparative effectiveness research study investigates whether adjuvant chemotherapy is associated with survival in patients with gynecologic cancer undergoing pelvic exenteration with pelvic lymph node metastasis.

OBJECTIVE:Early adverse outcomes after treatment for advanced ovarian cancer are often grouped as early relapse or death, although these events may reflect distinct mechanisms. We aimed to characterize early failure phenotypes and develop pragmatic clinical tools to stratify the risk of early death and early relapse. METHODS:This international multi-center real-world study included 3286 patients with advanced ovarian cancer treated within the SUROVA network. Early death was defined as death within 12 months and early relapse as recurrence within 12 months. Baseline, surgical, and post-operative variables were analyzed. Two clinical scores were developed: the Early Lethality Risk Score and the Early Relapse Risk Score. Discrimination was assessed using areas under the curve and compared descriptively with corresponding multi-variable logistic regression models. RESULTS:Within 12 months, 193 patients (5.9%) died; among patients alive at 12 months, 441 (15.8%) experienced early relapse and 2357 (84.2%) had no early adverse event. Early death and documented early relapse showed partial overlap: 45.6% of early deaths occurred without documented progression. Early death was associated with older age, impaired performance status, advanced stage, incomplete cytoreduction, and major post-operative complications. Early relapse among patients who survived 12 months was mainly associated with tumor burden and residual disease. The Early Lethality Risk Score showed acceptable discrimination (area under the curve 0.709, 95% confidence interval 0.666 to 0.752), with modest discrimination for the Early Relapse Risk Score (area under the curve 0.636, 95% confidence interval 0.609 to 0.662). CONCLUSIONS:Early failure in advanced ovarian cancer comprises clinically distinguishable early outcome patterns, with early death more strongly associated with vulnerability and post-operative morbidity, and early relapse among patients who survived 12 months more closely associated with disease burden and residual disease.

Objective: We aimed to compare the oncological outcomes of patients with bilateral sentinel lymph nodes (SLNs) detection and removed with those who underwent pelvic lymphadenectomy (PLA) in addition to bilateral SLNs removal. Methods: This multicenter, retrospective study included cases of endometrioid type, grade I-II endometrial cancer, in which bilateral SLNs were detected and removed. Patients who had only bilateral SLNs detected and removed (group I) and patients who had bilateral SLNs detected and removed and subsequent additional bilateral PLA (group II) were included in the evaluation. Results: In group I (n=216), SLN metastasis rate was 5.5% and in group II (n=251), it was 10.3%. The low-volume disease detection rate was 4.6% in group Iand 4.8% in group II. In group II, in patients with SLN macrometastasis had also 28.6% non-SLN macrometastasis. No false-negative results occurred in group II. Recurrence was detected 1.8% in group Iand 5% in group II; however, there was no significant difference (p=0.083). Disease-free survival and overall survival, were almost same between the groups (hazard ratio [HR]=2.11; 95% confidence interval [CI]=0.681-6.588; p=0.187) and (HR=1.531; 95% CI=0.392-5.975; p=0.537), respectively. Conclusion: SLN mapping, ultrastaging, and immunohistochemical staining can identify low-volume metastases that may not be identified with classic lymphadenectomy and hematoxylin & eosin staining. It has been observed that adding PLA beyond SLN mapping did not provide an additional positive contribution to survival. For endometriod type grade I-II patients, detection of bilateral SLNs in both hemipelvis only, if detectable, is an adequate approach.

AIM:This study evaluated predictors and treatment of isolated vulvar recurrence (IVR) in patients with stage I-II tumors locally confined to the vulva. METHODS:We retrospectively collected data from patients with stage I-II vulvar squamous cell carcinoma (VSCC) who underwent surgery for vulvar cancer between 2005 and 2021. The IVR group comprised patients with stage I-II tumors at the time of initial diagnosis who developed recurrence confined to the vulvar region after initial treatment. RESULTS:This study included 416 patients with early-stage (stage I-II) VSCC. IVR was developed in 67 (16.1%) patients; the remaining 349 patients were included in the control group. Independent predictors of IVR were depth of invasion, perineural invasion, and positive surgical margins. Among patients with tumors confined to the vulva at the time of initial diagnosis, the 5-year overall survival rates were 59.0% and 87.0% in the IVR and control groups, respectively (P < 0.001). In the IVR group, the cumulative rates of local relapse were 38.8% in the first year, 58.2% in the second year, and 74.6% in the third year. CONCLUSION:Independent predictors of IVR in early-stage VSCC were depth of invasion, perineural invasion, and positive surgical margins. Approximately two-thirds of local recurrences occurred in the first 3 years after treatment.

OBJECTIVE: To collect data from patients undergoing pelvic exenteration in recent clinical practice. The primary aim was 5-year disease-free survival. Secondary aims were 5-year overall survival, patterns of recurrence, identification of subgroups at higher risk of recurrence and death, survival associated with lymph node metastasis, and development of a prognostic score. METHODS: This was a retrospective, multicenter, international study conducted in tertiary national gynecologic oncology referral centers. Inclusion criteria included cervical, vaginal, vulvar, or endometrial cancer; anterior or total pelvic exenteration performed between January 2005 and March 2023; curative or palliative intent; and with or without laterally extended endopelvic or pelvic resection. Patients were excluded if they underwent posterior pelvic exenteration only or if preoperative computed tomography (CT), positron emission tomography (PET)–CT, or PET was not performed. A prognostic score was developed that was based on multivariable analysis. RESULTS: Eight hundred sixty-two patients were included. Surgical margins were tumor free in 676 (78.4%). In patients treated with curative intent, total pelvic exenteration, positive surgical margins, and presence of lymphovascular space invasion were independently associated with worse disease-free survival. Performance of lymphadenectomy was associated with better disease-free survival. Total pelvic exenteration, positive surgical margins, and presence of lymphovascular space invasion were factors independently associated with decreased overall survival. Performing pelvic exenteration at time of persistent (instead of recurrent) disease negatively affected overall survival. Prognostic score identified four risk groups with a 5-year disease-free survival of 43.7%, 24.9%, 22.2%, and 8.0% ( P <.001). The 5-year overall survival in the four risk groups was 54.3%, 40.4%, 24.0%, and 4.3% ( P <.001). The most frequent sites of recurrence were distant in 166 patients (32.1%). The 5-year disease-free survival and cancer-specific survival in patients with para-aortic lymph node metastasis were significantly worse compared with those in patients with pelvic-only metastatic nodes or with negative nodes ( P =.002 and P <.001, respectively). CONCLUSION: Independent factors associated with worse disease-free survival and overall survival and subgroups of patients at higher risk of recurrence and death were identified. A multivariable prognostic score was developed that can be used for patient counseling and surveillance strategies and for future prospective studies.

OBJECTIVE:This study aimed to assess intra-operative, short-term, and long-term morbidity and develop a score predicting post-operative complications after pelvic exenteration for gynecologic cancer. METHODS:This was a retrospective, multi-center, international study conducted in tertiary referral centers for gynecologic oncology. The inclusion criteria included cervical, vaginal, vulvar, or endometrial cancer; anterior/total pelvic exenteration performed between January 2005 and March 2023; curative/palliative intent; with or without laterally extended endopelvic/pelvic resection. Logistic regression adjusted for co-variables and a score predictive of severe post-operative complications based on the multi-variable analysis were developed. RESULTS:A total of 862 patients were included. Seven patients (0.8%) had severe intra-operative complications, and no patient experienced intra-operative death. A total of 225 patients (26.1%) had severe early post-operative complications and 27 (3.1%) died within 30 days. The most frequent severe early post-operative complications were pelvic abscess/collection (23.4%) and urostomy leak/fistula (13.4%). A total of 87 patients (10.1%) had severe late post-operative complications, and 16 patients (1.8%) died between 31 and 180 days. The most frequent severe late post-operative complications were pelvic abscess/collection (21.6%) and benign ureteric stricture (13.5%). Risk factors independently associated with severe early and late post-operative complications were no previous recurrences, American Society of Anesthesiologists score >1, total pelvic exenteration, infra-levator pelvic exenteration, laterally extended endopelvic/pelvic resection; and infra-levator pelvic exenteration and laterally extended endopelvic/pelvic resection, respectively. The COREPEX predictive score identified 4 groups with significantly different risk of severe post-operative complications (p < .001). CONCLUSIONS:Patients undergoing anterior or total pelvic exenteration have a low risk of intra-operative but a remarkable risk of major post-operative complications. No intra-operative death was recorded, and post-operative mortality was low. The COREPEX score predicting the risk of post-operative complications can be used to counsel patients and for future studies.

OBJECTIVE:To evaluate the presence of gynecologic pathologies accompanying adenomyosis among the hysterectomy specimens performed for various gynecologic indications. METHODS:This multicenter retrospective cohort study included women who underwent hysterectomy for various gynecologic indications and were diagnosed with adenomyosis at tertiary care centers. Eligible women were classified into two groups based on histopathologic results: Group 1-patients with only adenomyosis (n = 102) and Group 2-patients with adenomyosis and other gynecologic pathologies (n = 1353). Demographic and clinical characteristics, ultrasound examinations, and pathology reports were collected from medical records, and differences between the groups were assessed regarding clinical and demographic data, preoperative evaluations, and surgical characteristics. RESULTS:A total of 1455 patients were included. The adenomyosis-only group was significantly older than the group with other gynecologic pathologies. The most common coexisting condition was myoma uteri, found in 586 patients (43.3%), followed by cancer and endometrial polyp. Myoma uteri was the most common comorbidity in premenopausal women, but cancer was more prevalent in postmenopausal patients. The mean endometrial thickness was less in the adenomyosis-only group (6.5 ± 4.7 versus 8.0 ± 7.1 mm, P = 0.032). Adenomyosis was more frequent in patients with menstrual irregularities compared with pelvic pain and postmenopausal bleeding. Conversely, cancer was significantly more common in patients with postmenopausal bleeding. Overall, 351 (24.1%) patients were diagnosed with cancer, with endometrial cancer being the most common (n = 218, 62.1%). CONCLUSIONS:Our findings suggest that adenomyosis is frequently associated with conditions such as myoma uteri, endometrial polyps, and endometrial cancer.

ObjectiveTo compare the oncologic and perioperative outcomes of minimally invasive pelvic exenteration versus the conventional open approach in patients with gynecologic malignancies.MethodsThis was an international, multicenter, retrospective study including patients with cervical, vaginal, vulvar, or endometrial cancer who underwent anterior or total pelvic exenteration between January 2005 and March 2023. A propensity score matching(PSM) analysis was performed to reduce allocation bias. The primary endpoint was recurrence-free survival, while cancer-specific survival(CSS) and perioperative outcomes were evaluated as secondary endpoints.ResultsA total of 862 patients were analyzed, of whom 83 (9.6%) underwent minimally invasive surgery. After PSM, recurrence-free survival was comparable between the two groups (median 19 vs. 11 months, p=0.262), as was cancer-specific survival (CSS) (median 46 vs. 27 months, p=0.770). In multivariate analysis, positive surgical margins were independently associated with both shorter recurrence-free(HR 1.668, p<0.001) and cancer-specific survival (HR 1.591, p=0.004). Total pelvic exenteration was associated with reduced recurrence free survival(HR 1.290, p=0.020), while performing pelvic exenteration in the recurrent setting (HR 1.972, p=0.042) and tumor diameter greater than 5 cm (HR 1.412, p=0.013) were associated with shorter cancer specific survival. The minimally invasive approach resulted in significantly lower blood loss (700 versus 500ml, p<0.001) and shorter hospital stay (17 versus 12 days: p=0.006), although with longer operative time(360 versus 512 minutes, p<0.001).ConclusionIn this large, multicenter, propensity score-matched analysis, minimally invasive pelvic exenteration showed no statistically significant difference in oncologic outcomes compared with the traditional open approach, while providing some perioperative advantage. However, larger scale studies higher power would be necessary to conclude about safety and improvement in quality of life of the minimally invasive approach in this setting.

OBJECTIVE:To identify molecular subgroups in endometrioid endometrial cancer (EEC), evaluate their association with clinicohistopathological characteristics, and define low-intermediate risk groups by integrating these parameters. METHODS:This retrospective-cohort study included 1,040 patients who underwent surgery between January 2000 and June 2022. Among 900 EEC cases, 72 recurred. Patients with tumor recurrence (n=62) and those without (n=52) were matched. POLE exons 9-14 were examined using Sanger sequencing. p53 and mismatch repair (MMR) protein expression were assessed via immunohistochemistry. RESULTS:The molecular subgroups were POLE mutation (POLE-mut) 5%, mismatch repair-deficient (MMR-d) 43%, p53 mutation (p53-mut) 5%, and non-specific molecular profile (NSMP) 42%. 5% of cases displayed multiple molecular mutations. POLE-mut were more prevalent in high-grade tumors (p=0.026). MMR-d tumors exhibited higher rates of lymphovascular space invasion and myometrial invasion ≥50% (p=0.032, p=0.020). No recurrences occurred in POLE-mut tumors (p=0.002), while MMR-d was significantly associated with recurrence (p=0.002). Median disease-free survival (DFS) for MMR-d, p53-mut, and NSMP were 34, 49, and 107 months, respectively. Median overall survival (OS) for these groups was 128, 102, and 181 months. Multivariate Cox-regression analysis employing the Backward-Stepwise method identified stage as the strongest predictor of DFS, and grade and stage as predictors of OS. CONCLUSION:POLE mutations were linked to the most favorable molecular prognostic factor. NSMP cases showed the longest DFS and OS, while p53-mut had the shortest OS. Except for POLE, molecular features alone were insufficient for establishing risk groups, highlighting the continued importance of histopathology in EEC management.

OBJECTIVE:This research was undertaken to identify risk factors for the involvement of sentinel lymph nodes (SLNs) in cases of endometrial cancer. METHODS:From February 2016 to April 2021, the cases of 874 women with endometrial cancer treated with the SLN algorithm at 11 institutions were analyzed in this retrospective study. Clinical and pathologic data were reviewed, and logistic regression was applied to identify predictive factors for SLN involvement. RESULTS:After the exclusion of 81 patients, the remaining cohort of 793 patients was analyzed. The involvement of SLNs occurred in 9.2% of these cases (n = 73). In univariate analysis, the risk of SLN involvement was seen to be significantly higher among patients aged >60 years and those with high-grade tumors, non-endometrioid histology, lymphovascular space invasion, deep myometrial invasion, tumor diameters of ≥2 cm, and cervical stromal invasion. Multivariate analysis identified the occurrence of deep myometrial invasion (OR 2.42, 95% CI 1.29 to 4.56; p = .006), cervical stromal invasion (OR 2.18, 95% CI 1.13 to 4.21; p = .020), and lymphovascular space invasion (OR 7.27, 95% CI 3.82 to 13.81; p < .001) as risk factors independently predictive of SLN involvement in the treatment of endometrial cancer. CONCLUSION:Deep myometrial invasion, cervical stromal invasion, and lymphovascular space invasion were found to be independently predictive of the involvement of SLNs in cases of endometrial cancer. For cases in which SLN dissection was not or could not be performed, the identified independent risk factors are crucial for guiding adjuvant therapy.

Objective The aim of this study was to investigate the impact of adjuvant treatments, factors influencing recurrence, and survival data in patients with 2023 International Federation of Gynecology and Obstetrics (FIGO) stage IIB endometrial cancer. Methods A retrospective analysis was conducted on patients with endometrial cancer who underwent surgery between 2005 and 2022 at seven different centers in Turkey. Demographic, clinicopathological, and survival data were collected and analyzed. Results Among 7323 patients, 565 (7.7%) were classified as 2023 FIGO stage IIB based on pathological results. Of 565 patients, 214 were followed without receiving adjuvant treatment, while 335 (95.4%) received adjuvant radiotherapy, and 16 (4.6%) received radiotherapy and chemotherapy. The locoregional recurrence rate was higher in patients with a tumor size >4 cm (p=0.038) and myometrial invasion >50% (p=0.045). In patients with distant metastasis, the recurrence rate was lower in those with myometrial invasion <50% compared with myometrial invasion ≥50% (p=0.031). The impact of adjuvant treatment on endometrial cancer patients revealed no significant differences for both disease free survival (p=0.85) and overall survival (p=0.54). Subgroup analyses showed that in patients with deep myometrial invasion, adjuvant treatment was associated with a significant increase in overall survival (p=0.044), but there was no effect on disease-free survival (p=0.12). Conclusions Patients with stage IIB endometrial cancer with myometrial invasion ≥50% were more likely to have locoregional and distant metastases. Adjuvant radiotherapy or chemoradiotherapy did not demonstrate an overall survival benefit in these patients.

Introduction: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3-4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. Methods: Out of 219 patients with advanced epithelial ovarian cancer, 123 patients received 3-4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterward, laparotomy was performed for interval cytoreductive surgery. Results: No statistically significant difference was found for DFS and OS of the patients who received 3-4 cycles and those who received 6 cycles of NACT (HR: 1.047, 95.0% CI [0.779-1.407]; p: 0.746 for DFS, and HR: 1.181, 95.0% CI [0.818-1.707]; p: 0.368 for OS). Evaluating 123 patients who received 3-4 cycles of NACT, 87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients (29.3%) with any residual tumor (HR: 1.830, 95.0% CI [1.194-2.806]; p: 0.003 for DFS, and HR: 1.946, 95.0% CI [1.166-3.250]; p: 0.009 for OS). 96 patients who received 6 courses of NACT were evaluated; 63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR: 1.716, 9 5.0% CI [1.092-2.697]; p: 0.010 for DFS, and HR: 1.921, 95.0% CI [1.125-3.282]; p: 0.013 for OS). Conclusion: In patients with advanced ovarian cancer, there is no significant difference in DFS and OS between 3 and 4 cycles or 6 cycles of NACT. The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT.