Stefano Fucina

Probe-Based Confocal Laser Endomicroscopy in Gynecologic Surgical Oncology: Intraoperative Insights to Guide Surgical Resection

Ovarian cancer is a leading cause of cancer-related death in women. Cytoreductive surgery is the cornerstone of treatment, but frequently requires extensive surgical procedures. In vivo pCLE images and subsequent biopsies were acquired from various anatomical sites after injection of fluorescein. Each endomicroscopic sequence was analyzed by dedicated investigators highly experienced in pCLE imaging and compared with the histology of the corresponding specimen. Normal tissues exhibited uniform stromal fibers, consistent cellular architecture, and regular vascularization. In contrast, malignant nodules were identified by fluorescein leakage, reflecting abnormal vessel permeability and highlighting clusters of neoplastic cells. Preliminary data from our observations indicate a substantial concordance between pCLE findings and histology. pCLE is a promising intraoperative tool for real-time cellular analysis.

Evaluating the role of secondary surgery and PARP inhibition in platinum-sensitive ovarian cancer relapse

To assess the benefit of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC), and to evaluate how survival outcomes are influenced by second-line PARP inhibitor maintenance therapy. This retrospective study included 52 patients with platinum-sensitive recurrent EOC treated at the National Cancer Institute of Aviano, Italy, between 2015 and 2022. Patients received either SCS followed by chemotherapy (SCS+CT group) or chemotherapy alone (CT-only group). The primary endpoints were progression-free survival (PFS) and post-recurrence survival (PRS). Secondary analyses explored the impact of second-line PARPi maintenance on survival outcomes within each treatment group. Patients in the SCS+CT group experienced significantly longer PFS compared to those in the CT-only group (median 19.2 vs. 10.0 months, p=0.007). Among patients receiving PARPi maintenance, the benefit was even more pronounced: median PFS was 40.3 months in the SCS+CT group versus 21.9 months in the CT-only group (p=0.026). A non-significant trend toward improved PRS was observed in the SCS+CT group (48.3 vs. 36.0 months, p=0.23). PARPi maintenance was associated with longer PRS in both treatment arms (p=0.0056 for SCS+CT; p=0.033 for CT-only). In patients with platinum-sensitive recurrent EOC, SCS combined with chemotherapy significantly improves PFS, particularly when followed by second-line PARPi maintenance. These findings support the role of SCS in carefully selected patients and emphasize the synergistic effect of integrating surgical and molecularly targeted strategies.

Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target. We highlight studies on the mechanisms through which TOP2A contributes to tumor progression and recurrence. Additionally, we evaluate the clinical implications of targeting TOP2A, including the use of TOP2A inhibitors and their combination with novel drugs. We provide a comprehensive overview of the current understanding and future directions for targeting TOP2A in the management of EOC.

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.

Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.