Basilio Pecorino

Exploring the impact of exercise on women with ovarian cancer: A call for more methodologically standardized RCTs to enable a realistic systematic review

Ovarian cancer remains a leading cause of mortality among gynecological malignancies, often diagnosed at advanced stages due to nonspecific symptoms and limited screening tools. Standard treatment, including cytoreductive surgery and chemotherapy, can cause fatigue, physical dysfunction, and psychological distress, impacting quality of life. Exercise interventions have shown potential to mitigate these effects, but inconsistent methodologies in randomized controlled trials (RCTs) limit reliable conclusions and clinical integration. A systematic review was conducted following PRISMA guidelines. RCTs assessing physical exercise effects on women with ovarian cancer were included, excluding pilot trials, reviews, and combined therapies. Data extraction and GRADE assessments were performed by two independent reviewers, and a narrative synthesis was conducted due to study heterogeneity. Eleven RCTs were analyzed, covering aerobic, resistance, and yoga interventions. Findings indicated improvements in physical function, fatigue, and psychological outcomes, such as reduced depressive symptoms and cognitive enhancements. Patients adhering to ≥150 min of moderate-intensity exercise per week experienced the most consistent benefits. Preoperative walking expedited recovery, though significant heterogeneity in study protocols precluded meta-analysis. Evidence supports the feasibility and benefits of exercise across ovarian cancer stages. However, inconsistency in exercise intensity, duration, and reporting hinders the development of standardized protocols. Compared to cardiological rehabilitation, ovarian cancer exercise guidelines remain underdeveloped, emphasizing the need for tailored, evidence-based interventions. Exercise interventions can improve physical and mental health in ovarian cancer patients. Standardized RCTs are urgently needed to establish robust exercise protocols and enable clinical implementation, enhancing survivorship outcomes and quality of life.

Endometrial carcinosarcoma without myoinvasion

Uterine carcinosarcoma without myoinvasion, limited to the endometrial lining/polyp or with no residual uterine disease at the time of hysterectomy, is extremely uncommon, with unknown oncologic outcomes. Thus, this study aimed to evaluate the long-term outcomes of patients with carcinosarcoma without myoinvasion. Patients with International Federation of Gynecology and Obstetrics 2009 stage IA carcinosarcoma without myoinvasion who underwent surgery from December 1998 to January 2023 were identified from 11 centers worldwide. Patients were classified by tumor status (limited to the endometrium, limited to polyp, no residual disease in the hysterectomy specimen) and by type of adjuvant therapy (chemotherapy vs no chemotherapy). Survival analysis follow-up was limited to the first 5 years after surgery. Of 97 patients included, 28 (28.9%) had disease confined to a polyp, 55 (56.7%) to the endometrium, and 14 (14.4%) had no residual disease in the hysterectomy specimen. Patients received observation only (n=16, 16.5%), vaginal brachytherapy alone (n=14, 14.4%), external beam radiation therapy ± vaginal brachytherapy (n=5, 5.2%), chemotherapy ± vaginal brachytherapy (n=51, 52.6%), and chemotherapy and external beam radiation therapy ± vaginal brachytherapy (n=7, 7.2%), whereas adjuvant therapy was unknown in 4 patients (4.1%). A total of 29 patients (29.9%) recurred, mostly with a distant pattern of relapse. The 5-year recurrence-free survival was 63.5% (95% CI 53.4% to 75.4%) and the overall survival was 72.0% (95% CI 62.6% to 82.9%). The median follow-up for patients without recurrence was 56.9 months (interquartile range; 21.8-72.9). No significant differences were observed in recurrence-free survival and overall survival based on status of the tumor (p=.99 and p=.43, respectively). The difference in recurrence-free survival and overall survival was not statistically significant based on the receipt of chemotherapy (p=.08 and p=.07, respectively). Patients with carcinosarcoma without myoinvasion have a poor prognosis, with a high recurrence rate with distant pattern. The use of chemotherapy did not achieve statistical significance but may be limited by our small series.

Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Evaluation of Surgical Outcomes of Abdominal Radical Hysterectomy and Total Laparoscopic Radical Hysterectomy for Cervical Cancer: A Retrospective Analysis of Data Collected before the LACC Trial

Although a surgical approach is one of the key treatments for stages IA1-IIA2, results of the Laparoscopic Approach to Cervical Cancer (LACC) published in 2018 radically changed the field, since minimally invasive surgery was associated with a four-fold higher rate of recurrence and a six-fold higher rate of all-cause death compared to an open approach. We aimed to evaluate surgical outcomes of abdominal radical hysterectomy (ARH) and total laparoscopic radical hysterectomy (TLRH) for cervical cancer, including data collected before the LACC trial. In our retrospective analysis, operative time was significantly longer in TLRH compared to ARH (p < 0.0001), although this disadvantage could be considered balanced by lower intra-operative estimated blood loss in TLRH compared with ARH (p < 0.0001). In addition, we did not find significant differences for intra-operative (p = 0.0874) and post-operative complication rates (p = 0.0727) between ARH and TLRH. This was not likely to be influenced by age and Body Mass Index, since they were comparable in the two groups (p = 0.0798 and p = 0.4825, respectively). Finally, mean number of pelvic lymph nodes retrieved (p = 0.153) and nodal metastases (p = 0.774), as well as death rate (p = 0.5514) and recurrence rate (p = 0.1582) were comparable between the two groups. Future studies should be aimed at assessing whether different histology/grades of cervical cancer, as well as particular subpopulations, may have significantly different outcomes using minimally invasive surgery or laparotomy, with or without neoadjuvant chemotherapy.

Homologous Recombination Deficiency (HRD) Scoring, by Means of Two Different Shallow Whole-Genome Sequencing Pipelines (sWGS), in Ovarian Cancer Patients: A Comparison with Myriad MyChoice Assay

High-grade serous ovarian cancer (HGSOC) patients carrying the BRCA1/2 mutation or deficient in the homologous recombination repair system (HRD) generally benefit from treatment with PARP inhibitors. Some international recommendations suggest that BRCA1/2 genetic testing should be offered for all newly diagnosed epithelial ovarian cancer, along with HRD assessment. Academic tests (ATs) are continuously under development, in order to break down the barriers patients encounter in accessing HRD testing. Two different methods for shallow whole-genome sequencing (sWGS) were compared to the reference assay, Myriad. All these three assays were performed on 20 retrospective HGSOC samples. Moreover, HRD results were correlated with the progression-free survival rate (PFS). Both sWGS chemistries showed good correlation with each other and a complete agreement, even when compared to the Myriad score. Our academic HRD assay categorized patients as HRD-Deficient, HRM-Mild and HRN-Negative. These three groups were matched with PFS, providing interesting findings in terms of HRD scoring and months of survival. Both our sWGS assays and the Myriad test correlated with the patient’s response to treatments. Finally, our AT confirms its capability of determining HRD status, with the advantage of being faster, cheaper, and easier to carry out. Our results showed a prognostic value for the HRD score.