Vito Chiantera

Hyperthermic Intraperitoneal Chemotherapy in Platinum-Sensitive Recurrent Ovarian Cancer: A Randomized Trial on Survival Evaluation (HORSE; MITO-18)

PURPOSE To investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to secondary cytoreductive surgery (SCS) without neoadjuvant chemotherapy has a benefit on progression-free survival (PFS), as opposed to SCS alone in patients with platinum-sensitive recurrent epithelial ovarian cancer (platinum-free interval, >6 months). METHODS This was a multicenter randomized phase III study. Random assignment was performed at the time of surgery in cases with residual tumor ≤0.25 cm. HIPEC with cisplatin (CDDP) 75 mg/m 2 for 60 minutes at 41.5°C was administered at the end of surgery in the experimental arm. Both groups received postoperative platinum-based chemotherapy. The primary end point was PFS. The safety profile and postrecurrence survival (PRS) were the secondary end points. RESULTS A total of 167 patients underwent random assignment, 82 patients to SCS plus HIPEC (experimental arm) and 85 to SCS alone (control arm). The median follow-up was 83 months (IQR, 64-102). The median PFS was 23 months (95% CI, 17 to 29) in the group that underwent surgery alone and 25 months (95% CI, 18 to 32) in the group that underwent cytoreductive surgery with HIPEC. The probability of PRS at 5 years was 61.6% (95% CI, 50.8 to 72.4) in the SCS group and 75.9% (95% CI, 66.5 to 85.3) in the SCS plus HIPEC group. The incidence of postoperative adverse events of any grade was similar between the two groups. CONCLUSION The addition of HIPEC to complete or nearly complete primary SCS did not confer a benefit in terms of PFS in patients with platinum-sensitive peritoneal recurrence.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Fertility-Sparing Treatments in Endometrial Cancer: A Comprehensive Review on Efficacy, Oncological Outcomes, and Reproductive Potential

Endometrial cancer (EC) affects 3–14% of women under 40 who wish to preserve their fertility. The standard treatment for EC is a hysterectomy with salpingo-oophorectomy. However, for those desiring fertility preservation, oral progestogens such as medroxy-progesterone acetate (MPA) or megestrol acetate (MA) are the most common therapies in Fertility-Sparing Treatment (FST). Other treatments include gonadotropin-releasing hormone agonist (GnRHa), levonorgestrel-releasing intrauterine system (LNG-IUS), and metformin plus progestin. This comprehensive review evaluates the best FST options for women with reproductive potential. PubMed, EMBASE, and Scopus were searched in June 2023 using specific keywords. Studies included in the review focused on patients with EC undergoing FST, with outcomes such as complete response rate (CRR), recurrence rate (RR), pregnancy rate (PR), and live birth rate. Eighteen studies met the inclusion criteria, involving 23,976 patients. In only-oral progestin trials, CRR ranged from 18% to 100%; RR ranged from 0% to 81.8%; Death Rate ranged from 0% to 3.6%. In studies combining oral progestin with LNG-IUS, CRR ranged from 55% to 87.5%; RR ranged from 0% to 41.7%; Death Rate was 0%. Most patients with Stage IA EC received MPA or MA. Fertility-related outcomes were reported in 15 studies. PR ranged from 4 to 44 patients in trials involving only oral progestins. When combining oral progestin with LNG-IUS, PR ranged from 1 to 46 patients. Progestin therapy, including oral MPA and MA, is considered safe and effective, with limited evidence supporting the use of LNG-IUS.

Hysteroscopic endometrial tumor localization and sentinel lymph node mapping. An upgrade of the hysteroscopic role in endometrial cancer patients

Given the growing interest in sentinel node mapping (SLN) biopsy in Endometrial Cancer (EC) patients, many efforts have been made to maximize the SLN bilateral detection rate. However, at present, no previous research assessed the potential correlation between primary EC location in the uterine cavity and SLN mapping. In this context, this study aims to investigate the possible role of intrauterine EC hysteroscopic localization in predicting SLN nodal placement. EC patients surgically treated from January 2017 to December 2021 were retrospectively analyzed. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and SLN mapping. During hysteroscopy, the location of the neoplastic lesion was described as follows: uterine fundus (comprising the most cranial portion of the uterine cavity up to the tubal ostium including the cornual areas), corpus uteri (from the tubal ostium to the inner uterine orifice), and diffuse (when the tumor invades more than 50% of the uterine cavity). Three hundred ninety patients met the inclusion criteria. The tumor pattern diffused to the whole uterine cavity was statistically associated with SLN uptake on common iliac lymph nodes (OR 2.4, 95%CI 1-5.8, p = 0.05). Patients'age is an independent factor associated with SLN failure (OR: 0.95, 95%CI 0.93-0.98, p < 0.001). The study showed a statistically significant association between EC hysteroscopically spread throughout the whole uterine cavity and SLN uptake at the common iliac lymph nodes. Furthermore, patient age negatively affected the SLN detection rate.

Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1-G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial. Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006). Substantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.

Nodal Assessment in Endometrial Atypical Hyperplasia

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25–50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. &lt;b&gt;&lt;i&gt;Design:&lt;/i&gt;&lt;/b&gt; This was a retrospective study. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (&lt;i&gt;p&lt;/i&gt; = 0.01), hypertension (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.01), and endometrial thickness ≥20 mm (&lt;i&gt;p&lt;/i&gt; = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29–6.48) in AUB, 2.7 (95% CI: 1.06–6.92) in hypertension, and 3.1 (95% CI: 1.19–7.97) in endometrial thickness ≥20 mm cases. &lt;b&gt;&lt;i&gt;Limitations:&lt;/i&gt;&lt;/b&gt; The present study has limitations inherent in its retrospective nature. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience

To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.

Minimally Invasive Surgery for Cervical Cancer: Should We Look beyond Squamous Cell Carcinoma?

Evaluation of survival and mortality in pelvic exenteration for gynecologic malignancies: a systematic review, meta-analyses, and meta-regression study

Pelvic exenteration is a radical surgery for advanced or recurrent pelvic tumors, requiring careful patient selection and a multi-disciplinary approach. Despite advancements, it remains high-risk, with limited data on outcomes. The present meta-analysis evaluates survival, mortality, and trends to clarify its role in gynecologic oncology. A systematic search was conducted in January 2025 to identify studies on pelvic exenteration outcomes for gynecologic malignancies. Studies with at least 10 patients reporting 5-year overall survival or 30-day mortality were included. Data extracted included patient and surgical characteristics, and a scoring system based on study design, sample size, and center volume was used to include high-quality studies (score ≥3). Poisson regression models were used to analyze the associations between predictors and outcomes, with results expressed as incidence rate ratios and a 95% CI. A total of 46 studies involving 4417 patients met the inclusion criteria. Most patients underwent pelvic exenteration for cervical cancer (N = 3183). Positive pelvic and aortic nodal involvement were key predictors of reduced 5-year overall survival, decreasing by 3.9% and 5.9% per 1% increase in nodal positivity, respectively. Pelvic wall involvement also significantly reduced survival by 15.9%. The 30-day mortality rate was 5.1%, with sepsis (27.2%) being the leading cause of death. Peri-operative mortality decreased significantly over time, with each year of publication associated with a 2.6% decrease in incidence rate. However, pelvic sidewall involvement and total exenteration increased 30-day mortality by 11.5% and 0.7%, respectively. Pelvic exenteration remains a viable but high-risk option for select patients with advanced gynecologic malignancies. Pre-operative assessment and multi-disciplinary planning are essential for optimizing outcomes.

Prognostic value of isolated tumor cells in sentinel lymph nodes in intermediate-risk endometrial cancer: results from an international, multi-institutional study

This study assessed oncologic outcomes of patients with intermediate-risk endometrioid endometrial cancer and isolated tumor cells (ITC) (≤0.2 mm or ≤200 cells) in sentinel lymph nodes (SLNs). Patients with SLN-ITC diagnosed between 2012 and 2019 were identified from 19 centers worldwide, while SLN-negative patients were identified at Mayo Clinic, Rochester between 2014 and 2018. Only patients with endometrioid endometrial cancer and intermediate-risk factors (low-grade endometrioid histology and myometrial invasion ≥50%; high-grade endometrioid histology and myometrial invasion <50%) were included. Oncologic outcomes were evaluated by grouping patients according to prognostic factors: SLN-ITC and lymphovascular space invasion (LVSI). SLN-ITC patients with post-operative observation or vaginal brachytherapy (VB) alone were compared with similar node-negative patients. Of the 166 patients included, those with simultaneous presence of SLN-ITC and LVSI were at higher risk of non-vaginal recurrence (HR 3.73 [95% CI 1.17 to 11.84], p = .01) compared with patients who were node-negative with no LVSI. Among the 122 patients (28 SLN-ITC, 94 node-negative) who underwent post-operative observation or VB alone, 1 isolated vaginal recurrence was documented in a node-negative patient, while non-vaginal recurrence occurred in 3 of 28 (10.7%) SLN-ITC and 7 of 94 (7.4%) node-negative patients. The median follow-up was 2.4 years (interquartile range; 1.8-3.0) among the remaining 25 ITC patients and 2.8 years (interquartile range; 0.8-4.2) among the remaining 87 node-negative patients. There was no difference in non-vaginal recurrence-free survival (SLN-ITC: 87.3% [95% CI 74.7% to 100.0%] vs node-negative: 82.2% [95% CI 69.1% to 97.9%], p = .46) or overall survival (SLN-ITC: 76.4% [95% CI 54.3 to 100.0] vs node-negative: 84.5% [95% CI 75.0 to 95.2], p = .28) between the 2 cohorts. In patients with endometrioid endometrial cancer and intermediate-risk factors (including patients who received chemotherapy/external beam radiotherapy), the combination of SLN-ITC and LVSI was associated with worse prognosis compared with patients with no risk factors or only 1 risk factor. In the sub-group of patients who received post-operative observation or VB alone, SLN-ITC did not worsen prognosis relative to node-negative patients.

Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. ClinicalTrials.gov: NCT06689956.

Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) in Ovarian Cancer Recurrence

The purpose of this study is to determine the role of surgery followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) versus surgery alone in patients with platinum-sensitive first recurrence of ovarian cancer. Moreover it is a prospective randomized multicenter trial, aimed to investigate the prognostic role of surgery plus HIPEC versus surgery alone in terms of progression free interval, overall survival, morbidity and mortality, second recurrence pattern, quality of life with EORTC QLQ-C30 and QLQ OV28 questionnaires.