Enrico Busato

Role of Age, Comorbidity, and Frailty in the Prediction of Postoperative Complications After Surgery for Vulvar Cancer: A Retrospective Cohort Study with the Development of a Nomogram

Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and frailty in predicting postoperative complications after vulvar cancer surgery and to develop a predictive nomogram. A retrospective cohort study was conducted, including patients who underwent surgery for vulvar cancer at two Italian institutions from January 2018 to December 2023. A logistic regression model for the rate of Clavien-Dindo 2+ 30-days complications was run, considering the age-adjusted Charlson Comorbidity Index (AACCI), body mass index (BMI), and frailty as exposures. Lesion characteristics and surgical procedures were considered as confounders. Among the 225 included patients, 50 (22.2%) had a grade 2+ complication. The predictive score of the nomogram ranged from 44 to 140. The AACCI (0–64 points) and BMI (0–100 points) were independently associated with a risk of complications. A nomogram including the AACCI and BMI predicts the risk of complications for patients undergoing surgery for vulvar cancer. The preoperative determination of the risk of complications enables surgical planning and allows a tailored peri- and postoperative management plan.

Exploring conservative management for cervical intraepithelial neoplasia grade 2 in organised cervical cancer screening programmes: a multicentre study in Italy

Cervical intraepithelial neoplasia grade 2 (CIN2) lesions may regress spontaneously, offering an alternative to immediate treatment, especially for women of childbearing age (15–45 years).We conducted a prospective multicentre study on conservative CIN2 management, with semiannual follow-up visits over 24 months, biomarkers’ investigation and treatment for progression to CIN3+ or CIN2 persistence for more than 12 months. Here, we assess women’s willingness to participate and adherence to the study protocol.The study was set in population-based organised cervical cancer screening.From April 2019 to October 2021, 640 CIN2 cases were diagnosed in women aged 25–64 participating in the screening programmes.According to our predefined inclusion and exclusion criteria, 228 (35.6%) women were not eligible; 93 (22.6%) of the 412 eligible refused, and 319 (77.4%) were enrolled. Refusal for personal reasons (ie, desire to become pregnant, anxiety, difficulty in complying with the study protocol) and external barriers (ie, residence elsewhere and language problems) accounted for 71% and 17%, respectively. Only 9% expressed a preference for treatment. The primary ineligibility factor was the upper age limit of 45 years. After enrolment, 12 (4%) women without evidence of progression requested treatment, 125 (39%) were lost to follow-up (mostly after 6–12 months) and 182 (57%) remained compliant. Remarkably, 40% of enrolees did not fully adhere to the protocol, whereas only 5% (20/412) of the eligible women desired treatment.Our study demonstrates a good acceptance of conservative management for CIN2 lesions by the women, supporting its implementation within cervical screening programmes.

Predictive biomarkers for regression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2: A prospective multicenter study in Italy

Abstract Cervical intraepithelial neoplasia grade 2 (CIN2) can spontaneously regress in a sizable proportion of cases. The aim of this prospective multicenter cohort study was to identify the biomarkers associated with a high probability of regression. A total of 319 women aged 25–45 years fulfilling predefined inclusion and exclusion criteria (full visibility of transformation zone and lesion; no previous history of CIN2+ or immune impairment) were enrolled and subjected to active surveillance for 24 months. HPV genotyping, p16/ki67 expression, methylation status of FAM19A4/miR124‐2 genes, and cytology were evaluated at baseline. The probability of CIN2 regression according to the different biomarkers was evaluated through binomial logistic regression. At follow‐up, regression, persistence, and progression (evaluated on 294 women) were recorded in 165 (56%), 68 (23%), and 61 (21%) cases, respectively; no association with age was observed. Overall, 110 women underwent excisional treatment during follow‐up; 53 CIN2 and 50 CIN3+ were diagnosed. The probability of CIN2 regression significantly increased with early HPV negativity (odds ratio [OR] 6.45, 95% confidence intervals [CI] 1.68–42.6), no p16/ki67 expression (OR 2.49, 95%CI 1.38–4.52), and unmethylated status (OR 2.12, 95%CI 1.09–4.20). Our results indicate that active CIN2 surveillance could be implemented for women up to 45 years, after selection according to anatomo‐clinical criteria and biomarker status. To improve feasibility, the biomarkers can be used sequentially, taking advantage of the HPV genotyping available in primary screening tests, and eventually refining the selection by using the other biomarkers in selected subgroups.