A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer.

OBJECTIVE: To compare the risk class attribution with molecular classification unknown to those with molecular classification known, according to the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) 2020 guidelines on endometrial cancer, with a focus on risk group migration. Additionally, to evaluate the capability of a novel molecular analysis algorithm to reduce the number of required tests. METHODS: We conducted a retrospective study including all consecutive patients with endometrial cancer undergoing surgery and comprehensive molecular analyses between April 2019 and December 2021. Molecular analyses including immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were performed to classify tumors as POLE-mutated (POLE), MMR-deficient (MMR-d), p53 abnormal (p53abn), or non-specific molecular profile (NSMP). The two risk classifications of the ESGO/ESTRO/ESP 2020 guidelines were compared to estimate the proportion of patients in which the molecular analysis was able to change the risk class attribution. We developed a novel algorithm where the molecular analyses are reserved only for patients in whom incorporation of the molecular classification could change the risk class attribution. RESULTS: A total of 278 patients were included. Molecular analyses were successful for all cases, identifying the four subgroups: 27 (9.7%) POLE, 77 (27.7%) MMR-d, 49 (17.6%) p53abn, and 125 (45.0%) NSMP. Comparison of risk class attribution between the two classification systems demonstrated discordance in the risk class assignment in 19 (6.8%, 95% CI 4.2% to 10.5%) cases. The application of our novel algorithm would have led to a reduction in the number of POLE sequencing tests by 67% (95% CI 61% to 73%) and a decrease of p53 immunohistochemistry by 27% (95% CI 22% to 33%), as compared with the application of molecular classification to all patients. CONCLUSION: Molecular categorization of endometrial cancer allows the reallocation of a considerable proportion of patients in a different risk class. Furthermore, the application of our algorithm enables a reduction in the number of required tests without affecting the risk classification.

Oncologic Outcomes of Robotic Radical Hysterectomy (RRH) for Patients with Early-Stage Cervical Cancer: Experience at a Referral Cancer Center.

PURPOSE: To evaluate oncologic outcomes of early stage cervical cancer patients who underwent robotic radical hysterectomy (RRH) in a referral center, a retrospective analysis was performed. METHODS: From January 2010 to December 2018, medical records of stage IA2-IIA1 cervical cancer patients, who underwent radical hysterectomy at our institute, were retrospectively reviewed. We focused our analysis on those who underwent RRH. RESULTS: A total of 198 patients were included in the final analysis. Median follow up was 52 months. At last follow-up, 188 (94.9%) women were disease-free, 9 (4.5%) had died, and 1 (0.5%) was alive with recurrent disease. At 4.5 years, PFS was 93.1% (SE ± 2.1) and OS was 95.1% (SE ± 1.8). Stratified by tumor size, PFS for tumor < 2 cm versus tumor ≥ 2 cm was statistically different (96.8% ± 2.3 and 87.9% ± 4.1 respectively, p = 0.01), as well as OS (100% and 89.8% ± 40 respectively, p = 0.01).Stratified by evidence of tumor at time of robotic surgery, PFS was statistically different in women with no residual tumor after conisation versus those with residual disease (100% ± 2.5 and 90.8% ± 2.8 respectively, p = 0.04). A recurrence occurred in 11 patients (5.6%). CONCLUSIONS: Based on our results, we could speculate that robotic approach, along with some technical precautions to avoid spillage, might be safe as primary treatment of early-stage cervical cancer, especially for tumor < 2 cm and in case of no evidence of disease at time of radical hysterectomy after previous conisation.

Conization in Early Stage Cervical Cancer: Pattern of Recurrence in a 10-Year Single-Institution Experience.

OBJECTIVE: The main objective of this study was to analyze the pattern of recurrence after conization and pelvic lymphadenectomy in early-stage cervical cancer (CC). METHODS: We retrospectively identified 60 patients with early-stage CC who referred to the European Institute of Oncology (IEO; Milan, Italy) for fertility-sparing surgery. All of them underwent conization and pelvic lymphadenectomy (one received neoadjuvant chemotherapy followed by simple trachelectomy because of the size of the tumor). RESULTS: In total, 54 patients were considered for final analysis; only 23 patients were entirely treated at IEO. Relapse occurred in 7 (13%) of 54 patients, and in 6 cases (86%) it was local. One patient experienced a pelvic lymph node recurrence (in a woman who conceived 4 months after conservative surgery). However, this was an atypical case for site and timing of recurrence with the consistent doubt that the nodal involvement was already present before conization. Thus, analyzing only IEO population, the recurrence rate was lower (9%), becoming 4% excluding the atypical case with nodal involvement. CONCLUSIONS: In our series, the relapse was mainly local (on the cervix). However, the pattern of recurrence and recurrence rates after conization and pelvic lymphadenectomy for early-stage CC are still unclear. Further studies, comparing conization with radical trachelectomy, are necessary to confirm that the adoption of this procedure in clinical practice is safe. Our data highlight that the management of such as a particular condition in dedicated and highly specialized centers is mandatory.

Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

BACKGROUND/AIM: Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. PATIENTS AND METHODS: A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. RESULTS: A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. CONCLUSION: Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed.