Sara Gandini

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.

External validation of the annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

The annual recurrence risk model (ARRM), developed by the Surveillance in Cervical Cancer consortium and endorsed by the European Society of Gynecological Oncology, predicts the annual risk of cervical cancer recurrence. However, it lacks an external validation, which we aimed to address in the current retrospective study. We included patients with pathology confirmed T1a to T2b cervical cancers who underwent radical surgery at the European Institute of Oncology, Milan from January 2010 to December 2022. Using the ARRM risk calculator, patients were assigned a score from 0 to 100 points, which allowed classification into 5 risk groups (0, 1-25, 26-50, 51-75, and 76-100 points). Differences in 5-year disease-free survival were evaluated through log-rank tests with pairwise comparisons. Annual risk of recurrence was calculated using conditional survival analysis. Overall, 411 patients with cervical cancers were included: 0 (0.0%) scored 0 points, 149 (36.3%) scored 1 to 25 points, 224 (54.5%) scored 26 to 50 points, 37 (9.0%) scored 51 to 75 points, and 1 (0.2%) scored 76 to 100 points. The patient from 76 to 100 points was excluded from further analyses. The 5-year disease-free survival rates were 96.3% (95% CI 90.0 to 98.6), 85.7% (95% CI 80.1% to 89.9%), and 66.6% (95% CI 47.3% to 80.2%) in groups 1 to 25, 26 to 50, and 51 to 75 points, respectively (p < .01). Compared with 26 to 50 and 51 to 75 points, the annual risk of recurrence was lower in the 1 to 25 points group, at around 1% from year 1 to 5. The ARRM tool confirmed its validity in stratifying cervical cancer into groups with significantly different disease-free survival rates in an independent large population from a tertiary center. The annual risk of recurrence should be carefully considered when tailoring follow-up, always taking into account the patient's perspective.

Platinum-based chemotherapy and PARP inhibitors for patients with a germline BRCA pathogenic variant and advanced breast cancer (LATER-BC): retrospective multicentric analysis of post-progression treatments

Patients with breast cancer (BC) harbouring a germinal BRCA pathogenic variant (gBRCA-PV) may have an enhanced sensitivity to platinum-based chemotherapy (PBC) and PARP inhibitors (PARPi). As reported in ovarian cancer, however, sensitivity and resistance to these treatments could partially overlap. In patients with a gBRCA-PV and advanced BC (aBC), it remains unclear whether prior exposure to PARPi/PBC affects tumour response to subsequent PBC/PARPi, respectively. We conducted a retrospective, multicentric study to investigate the clinical benefit of post-PBC PARPi and vice versa in patients with a gBRCA-PV and aBC. Patients included had received (neo)adjuvant PBC and then PARPi in advanced setting (group 1), PBC followed by PARPi (group 2) or PARPi followed by PBC (group 3), both in advanced setting. We reported median progression-free survival (mPFS) and disease control rate (DCR) in each group. A total of 67 patients from six centres were included. PARPi-mPFS in advanced setting was 6.1 months in patients in group 1 (N = 12), while PARPi-DCR was 67%. In group 2 (N = 36), PARPi-mPFS was 3.4 months and PARPi-DCR was 64%. Age  6 months were associated with longer PARPi-PFS; previous PBC-PFS > 6 months and PBC in first to second line were associated with longer PARPi-DCR. Patients in group 3 (N = 21) reported a PBC-mPFS of 1.8 months and a PBC-DCR of 14%. PARPi-PFS ≥ 9 months and PARPi-FI ≥ 6 months were associated with better PBC-DCR. Sensitivity and resistance to PARPi and PBC partially overlap in patients with a gBRCA-PV and aBC. Evidence of PARPi activity emerged in patients who progressed on previous PBC.