Antonino Ditto

Sentinel lymph node biopsy in endometrial cancer: When, how and in which patients

The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades.

Hysteroscopic versus cervical injection for sentinel node detection in endometrial cancer: A multicenter prospective randomised controlled trial from the Multicenter Italian Trials in Ovarian cancer (MITO) study group

During the last years, the role of sentinel lymph node mapping (SLNM) for endometrial cancer (EC) surgical treatment has increased in popularity. However, several controversies remain about different technical steps of SLNM. Thus, a randomised control trial was designed to compare cervical (CI) and hysteroscopic (HI) indocyanine green (ICG) injection for SLNM of newly diagnosed EC undergoing surgical staging. The primary end-point of the study was to compare these two techniques in terms of para-aortic detection rate. Patients with apparent stage I or II histologically confirmed EC undergoing surgery were included in the study. This randomised trial distinguished patients in two study groups according to two different techniques of ICG SLNM: CI versus HI injection. Patients who met the inclusion criteria were randomly assigned to CI or HI injection in a 1:1 ratio. The central randomisation system allocated patient randomisation numbers sequentially in the order in which the patients were enrolled. This randomised trial was not blinded for either patients or the surgeons. From March 2017 until April 2019, a total of 165 patients were randomised in this study: 85 (51.5%) in the CI group and 80 (48.5%) in the HI group. After randomisation, 14 (8.5%) patients were excluded from the study. Finally, 151 patients were included in the analysis: 82 (54.3%) in the CI group and 69 (45.7%) in the HI group. Hysteroscopy injection shows an ability to detect Sentinel nodes (SNLs) in the para-aortic area of about 10% greater compared with CI injection, although this difference did not reach statistical significance. The HI technique was superior in detecting isolated para-aortic SLNs (5.8% Versus 0%). The CI injection was correlated with higher SLN detection rates at the pelvic level compared with HI injection. Pelvic and overall detection was higher in the CI group. The present study supports the adoption of CI instead of HI injection because the former allows better identification of sentinel nodes (especially in the pelvic area). Detection of SLN in the para-aortic area was slightly higher in patients receiving a HI injection, but the difference with the CI route was not statistically significant.

The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution

The 2023 FIGO staging of endometrial cancer integrates tumor grade and histology along with molecular features that recognize the prognostic significance of p53 and POLE mutations, accounting for potential conflicts such as lymphovascular space invasion and subserosal invasion. In this single-institution retrospective study, data were collected on 229 endometrial cancer patients from January 2020 to September 2024 and re-stage them according to FIGO 2023 criteria. From FIGO stage 2009 IA, 70 patients do not cross stage (21 are FIGO 2023 IA1 and 49 IA2), 8 patients are upgraded to FIGO IC because of aggressive histotype; 1 is upstaged because of substantial LVSI, and 12 because of aggressive myoinfiltrating tumors (23 % of upstaging). From FIGO 2009 stage IB 34 patients remain in FIGO 2023 IB, while 5 become stage IIB (LVSI) and 27 IIC (aggressive myoinfiltrating), for a total of 32 upstages (48 % of upstaging). Within FIGO 2009 stage II, no proper upstage was possible. We observed a statistical correlation between stages and BMI, as well as between stages and age, for both FIGO 2009 (p = 0.009 and p < 0.001 respectively) and FIGO 2023 (p = 0.002 and p = 0.003 respectively) classifications. Additionally, a correlation was found between tumor grade and BMI (p = 0.02). The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice.

Are biomarkers expression and clinical-pathological factors predictive markers of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer?

To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy.

Age-specific predictors of cervical dysplasia recurrence after primary conization: analysis of 3,212 women

This study aimed to identify predictors of recurrence/persistence of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesion (r-CIN2+) after primary conization. Retrospective analysis involving all consecutive women having conization for CIN2+ between 1998 and 2018. The risk of r-CIN2+ was assessed using Kaplan-Meier and Cox models. Data of 3,212 women were retrospectively identified. After a mean follow-up of 47 (±22.2) months, 112 (3.5%) patients developed r-CIN2+. Mean time interval between prior conization and diagnosis of r-CIN2+ was 26.2 (±13.2) months. Via multivariate analysis, presence of high-risk human papillomavirus (HPV) types at the time of CIN2+ diagnosis, hazard ratio (HR)=3.40 (95% confidence interval [CI]=1.66-6.95) for HPV16/18 and HR=2.59 (95% CI=1.21-5.55) for HPV types other than 16/18, positive margins at primary conization, HR=4.11 (95% CI=2.04-8.26) and HPV persistence after conization, HR=16.69 (95% CI=8.20-33.9), correlated with r-CIN2+, independently. Considering age-specific HPV types distribution, we observed that HPV16/18 infection correlated to an increased risk of r-CIN2+ only in young women (aged ≤25 years; p=0.031, log-rank test); while in the older population (>25 years) HPV type(s) involved had not impact on r-CIN2+ risk (p>0.200, log-rank test). HPV persistence is the main factor predicting r-CIN2+. Infection from HPV16/18 has a detrimental effect in young women, thus highlighting the need of implementing vaccination against HPV in this population. Further prospective studies are warranted for tailoring clinical decision-making for post-conization follow-up on the basis of risk factors.

Recurrence patterns and prognostic factors in vulvar extramammary Paget’s disease: a 10-year single institution experience

Extramammary Paget's disease of the vulva is a rare intra-epithelial malignancy with a high propensity for multiple local recurrences. Surgical excision remains the treatment of choice in most of the cases. However, due to its rarity, treatment modalities and prognostic indicators are still debated. We aimed to evaluate the recurrence patterns and to identify clinical factors associated with risk of recurrence in women with this disease. Retrospective analysis of women treated for vulvar Paget's disease at a single institution from January 2014 to December 2024. Clinical-pathological features, treatment modalities, and factors potentially related to disease recurrence were analyzed. An additional analysis was conducted to identify factors potentially associated with the development of multiple subsequent recurrences over time. A total of 69 patients fulfilling the study inclusion criteria were considered. A wide vulvo-perineal-peri-anal involvement was observed in 39.1% of cases, with multifocal disease observed in 37.7% of cases. In total, 34 women (49.3%) developed recurrent disease, with a median disease-free survival of 59.6 months (95% CI 33.3 to 95.9). Multifocal disease at initial diagnosis was the only factor significantly associated with an increased risk of recurrence (OR 2.89, 95% CI 1.05 to 7.96, p = .04). In 32.4% of cases, the recurrence occurred in a vulvo-perineal or peri-anal area distinct from the original site. Multiple recurrences over time were observed in 33.3% of patients. Vulvar Paget's disease is associated with a substantial risk of recurrence, particularly in patients with multifocal disease. Recurrences often arise at new anatomical sites, which may be more appropriately defined as "second field" Paget's disease. Although surgery remains a feasible and safe approach even in the setting of recurrent disease, individualized therapeutic strategies are advisable to improve long-term outcomes in this challenging patient population.

The future of gynecologic oncologic surgery: a narrative review of current surgical trials

Recent advances in gynecologic oncology have driven a paradigm shift toward less invasive, more personalized surgical approaches. This narrative review critically examines key ongoing international trials investigating innovative surgical strategies across vulvar, cervical, ovarian, and endometrial cancers, with a focus on improving oncologic outcomes while minimizing morbidity. In vulvar cancer, trials are exploring the use of neoadjuvant chemotherapy and the replacement of inguinofemoral lymphadenectomy with chemoradiation in selected patients. For cervical cancer, large multicenter randomized trials are evaluating the oncologic safety of minimally invasive hysterectomy, surgical staging for para-aortic disease, and robotic-assisted surgery. In the contest of ovarian cancer, randomized trials are assessing the role of lymphadenectomy in early-stage disease, the optimal timing of cytoreductive surgery (primary versus interval), and the potential benefits of hyperthermic intraperitoneal chemotherapy, even in cases of platinum-resistant recurrence. For endometrial cancer, both observational and interventional studies are investigating sentinel lymph nodes mapping and robotic-assisted hysterectomy as alternatives to traditional staging procedures. Collectively, these trials underscore the growing importance of individualized treatment strategies guided by disease stage, histologic subtype, response to neoadjuvant therapy, and patient-specific factors. While minimally invasive techniques and surgical de-escalation appear promising for selected patient populations, critical questions remain regarding long-term oncologic safety, cost-effectiveness, and the consistency of practice across institutions. This narrative review synthesizes current evidence and outlines how the outcomes of these pivotal studies are expected to influence future guidelines in gynecologic cancer surgery.