Lucia Ribero

Lymphadenectomy in early-stage ovarian cancer: is there still a role?

The role of systematic pelvic and para-aortic lymphadenectomy in presumed early-stage ovarian cancer remains controversial due to the lack of high-quality prospective evidence. No therapeutic benefit has been confirmed for systematic lymphadenectomy during surgical staging for apparent early-stage ovarian cancer. Lymphadenectomy may improve progression-free survival but has demonstrated no impact on overall survival, except for clear cell ovarian cancer, where a potential survival benefit has been suggested in retrospective studies. Systematic lymphadenectomy retains a diagnostic role in identifying occult nodal metastases (9% to 30% across series) undetected on pre-operative imaging or intra-operative assessment. The decision to perform lymphadenectomy should be individualized based on several factors, including histological sub-type, tumor grade, stage, and biomarker profile. Key considerations include the anticipated risk of lymph node metastasis, the opportunity to tailor adjuvant treatment by either omitting chemotherapy or offering maintenance targeted therapy, peri-operative morbidity, long-term sequelae impacting quality of life (eg, lower limb lymphedema), and cost-effectiveness. Systematic lymphadenectomy is guideline-recommended for high-grade tumors, including high-grade serous, high-grade endometrioid, and clear cell histologies, whereas it can be omitted in low-grade endometrioid and expansile mucinous sub-types. Its significance in low-grade serous and infiltrative mucinous ovarian cancers remains unclear, although guidelines frequently advocate for lymphadenectomy in these cases. To optimize patient selection, large-scale prospective studies with proper stratification by histotype and molecular profile are required. Emerging approaches to lymph node assessment, such as sentinel lymph node biopsy, artificial intelligence-assisted pre-operative imaging, and liquid biopsy, hold promise for improving staging accuracy.

The prognostic impact of molecular classification in endometrial cancer that undergoes fertility-sparing treatment

No biomarkers are available to predict treatment response in patients with endometrial cancers who undergo fertility-sparing treatment. Therefore, we aimed to evaluate the prognostic role of molecular classification. Patients with endometrial cancer who underwent fertility-sparing treatment with progestins between 2005 and 2021 were retrospectively identified. Polymerase epsilon (POLE), TP53/p53, and mismatch repair (MMR) proteins were assessed to assign patients to molecular groups: POLE mutated (POLEmut), MMR deficient (MMRd), no specific molecular profile (NSMP), and p53 abnormal (p53abn). Treatment response was classified as complete, partial, stable disease, or progressive. Response at 6 months, best response, and recurrence after complete response were evaluated by molecular class. In total, 33 patients were assigned to a molecular class and included in the analysis. Molecular testing detected 3 POLEmut (9%), 3 MMRd (9%), 25 NSMP (76%), and 2 p53abn (6%); 0 of 3 POLEmut (0%), 0 of 3 MMRd (0%), 6 of 25 NSMP (24%), and 1 of 2 p53abn (50%) achieved complete response within 6 months. In terms of best response during the entire treatment period, 2 of 3 POLEmut (67%), 2 of 3 MMRd (67%), 18 of 25 NSMP (72%), and 1 of 2 p53abn (50%) showed complete response. After complete response was achieved, 1 of 2 POLEmut (50%), 2 of 2 MMRd (100%), 14 of 18 NSMP (78%), and 0 of 1 p53abn (0%) had a recurrence. Although the small number of patients limits our findings, a lower proportion of MMRd responded to progestins than of NSMP.

Predictors of recurrence in early-stage cervical cancer without adjuvant treatment after radical surgery

The role of adjuvant radiotherapy after radical surgery for early-stage cervical cancer is controversial in the absence of high-risk factors. This study aimed to evaluate predictors of recurrence in patients with early-stage cervical cancer undergoing observation after radical surgery. Patients with FIGO 2018 stage I cervical cancer who underwent radical surgery without adjuvant therapy at the European Institute of Oncology, IEO (Milan, Italy) between 2010 and 2023 were retrospectively identified. Patients with high-risk factors for recurrence (positive margins, parametria, or lymph nodes) were excluded. Recurrence-free survival following surgery was estimated using the Kaplan-Meier method. Log-rank test and Cox regression analyses were performed to assess predictors of recurrence. A total of 340 patients were identified: 7 (2.0 %) stage IA1, 31 (9.1 %) IA2, 191 (56.2 %) IB1, 108 (31.8 %) IB2, and 3 (0.9 %) IB3. Twenty-two (6.5 %) patients had a recurrence. The estimated 5-year recurrence-free survival for the overall cohort was 93.5 % (95 % CI, 89.9-95.8). On multivariate analysis, factors associated with a higher risk of recurrence included tumor size ≥2 cm (HR 3.04, 95 % CI 1.26-7.35; p = 0.01) and grade 3 (HR 2.76, 95 % CI 1.1-6.9; p = 0.03). In the absence of high-risk factors, the risk of recurrence in patients with early-stage cervical cancer who did not receive adjuvant treatment after radical surgery was low overall. Patients with individual risk factors such as tumor size ≥2 cm or tumor grade 3 may be at higher risk of recurrence. Further research is warranted to redefine risk groups and tailor adjuvant treatment based on timely clinicopathological risk factors.