Carmine Conte

Extending the timing for secondary cytoreductive surgery after second-line chemotherapy in relapsed ovarian cancer: the EXTENSION study

Relapse remains a major issue for patients with advanced epithelial ovarian cancer. Based on the DESKTOP III trial, international guidelines recommend secondary cytoreduction surgery when feasible before starting chemotherapy in platinum-sensitive relapsed ovarian cancer. Currently, neoadjuvant chemotherapy before secondary cytoreduction surgery is not advised outside of clinical trials. Recently, CHIPOR trial has shown the efficacy of secondary cytoreduction surgery with hyperthermic intra-peritoneal chemotherapy after neoadjuvant chemotherapy in an unselected population with platinum-sensitive relapsed ovarian cancer. The primary aim of this study was to assess the rate of potential delayed secondary cytoreduction surgery after 6 cycles of neoadjuvant chemotherapy. This retrospective, monocentric, observational study included patients with platinum-sensitive relapsed ovarian cancer deemed unsuitable for secondary cytoreductive surgery after evaluation by a multidisciplinary tumor board and/or diagnostic laparoscopy from January 2020 to December 2023. After 6 cycles of neoadjuvant chemotherapy, secondary cytoreduction surgery feasibility was evaluated by applying criteria for upfront secondary cytoreduction surgery in patients with at least a partial response at computed tomography scan. Overall, 522 patients with platinum-sensitive relapsed ovarian cancer were evaluated; 165 were considered unsuitable for upfront secondary cytoreduction surgery and received second-line chemotherapy. After 6 cycles of neoadjuvant chemotherapy, secondary cytoreduction surgery was considered feasible in 48 patients (29.1%, group A), while 117 patients (70.9%, group B) remained ineligible for surgery. Predictors of secondary cytoreduction surgery feasibility were analyzed. Multivariate analysis identified a favorable modeled CA125 elimination rate constant K score at second-line chemotherapy (OR 7.29, 95% CI 2.91 to 18.30, p < .001) as the only independent predictor. Patients eligible for delayed secondary cytoreduction surgery showed significantly longer progression-free survival 2 and post-relapse survival (median progression-free survival 2 12.5 vs 7.9, p < .001; median post-relapse survival: not reached vs 28.5, p = .002). In a real-life approach in a tertiary oncological center, we showed that around 30% of women with platinum-sensitive relapsed ovarian cancer, initially deemed unsuitable for secondary cytoreduction surgery, can potentially undergo delayed secondary cytoreduction surgery following a favorable response to 6 cycles of neoadjuvant chemotherapy.

Hereditary Women’s Cancer: Management and Risk-Reducing Surgery

Hereditary women’s syndromes due to inherited mutations result in an elevated risk of developing gynecological cancers over the lifetime of affected carriers. The BRCA 1 and 2 mutations, Lynch syndrome (LS), and mutations in rare hereditary syndromes increase this risk and require more effective management of these patients based on surveillance and prophylactic surgery. Patients need counseling regarding risk-reducing surgery (RRS) and the time required to perform it, considering the adverse effects of premenopausal surgery and the hormonal effect on quality of life, bone density, sexual activity, and cardiological and vascular diseases. Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard for BRCA-mutated patients. An open question is that of endometrial cancer (EC) risk in patients with BRCA1/2 mutation to justify prophylactic hysterectomy during RRSO surgical procedures. RRS provides a 90–95% risk reduction for ovarian and breast cancer in women who are mutation carriers, but the role of prophylactic hysterectomy is underinvestigated in this setting of patients. In this review, we evaluate the management of the most common hereditary syndromes and the benefits of risk-reducing surgery, particularly exploring the role of prophylactic hysterectomy.

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.