Investigator
University Of Udine
Surgical timing in advanced ovarian cancer during the TRUST trial era: A systematic review, meta-analysis and study-level meta-regression of randomized controlled trials
The best surgical timing for advanced epithelial ovarian cancer, whether primary debulking surgery or interval debulking surgery, remains debated. Recent data, including the preliminary ones from TRUST trial, necessitates an updated critical evaluation. A systematic search of PubMed identified only randomized controlled trials comparing interval debulking surgery versus primary debulking surgery in patients with newly diagnosed advanced ovarian cancer. Primary outcomes included overall survival (OS) and progression-free survival (PFS). A random-effects meta-analysis, meta-regression, cumulative synthesis, and leave-one-out influence analysis were performed. A total of 2303 patients were included. Compared to primary debulking surgery, interval debulking surgery was associated with lower rates of postoperative complications (OR = 0.37; 95 % CI: 0.18-0.79; P = 0.01) and mortality (OR = 0.23; 95 % CI: 0.09-0.57; P = 0.002). Meta-analysis showed higher rates of complete cytoreduction with interval debulking surgery (OR = 3.84; 95 % CI: 2.14-6.91; P < 0.00001) and lower rates of macroscopic residual disease (OR = 0.20; 95 % CI: 0.13-0.30; P < 0.00001). Pooled data revealed no significant difference in OS (HR = 0.95; 95 % CI: 0.87-1.04; P = 0.26) or PFS (HR = 0.94; 95 % CI: 0.85-1.03; P = 0.16). Subgroup analyses by stage and residual disease confirmed similar survival outcomes. The meta-regression results suggested that even in trials with very high complete cytoreduction rates, no clinically meaningful OS benefit was observed for upfront surgery. In conclusion, interval debulking surgery offers comparable survival outcomes to primary debulking, with reduced perioperative morbidity and mortality, supporting its role as a valid surgical alternative. PROSPERO REGISTRATION NUMBER: CRD420251105308.
Molecular biology as a driver in therapeutic choices for ovarian cancer
Simple hysterectomy versus radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis
This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer. We systematically searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate [OR = 0.88; 95% CI (0.50, 1.57); P = 0.68] and Overall Survival (OS) [OR = 1.23; 95% CI (0.69, 2.19), P = 0.48]. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury [OR = 0.28; 95% CI (0.08, 0.94), P = 0.04] and bladder disfunction [OR = 0.10; 95% CI (0.02, 0.53), P = 0.007] of the RH group were higher compared to the SH group. This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.
Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer
The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.
