Introduction The standard treatment for epithelial early stage ovarian cancer (eEOC) includes laparotomic surgical staging, according to ESGO-ESMO guidelines. In the last decade, many investigators have assessed the safety and feasibility of minimally invasive surgery (MIS) staging in properly selected patients. However, survival data related to different surgical approaches (open versus MIS) are extremely limited. The aim of this study is to analyze the long-term oncological outcomes in eEOC patients treated with MIS. Materials and methods This is a multicenter observational retrospective study conducted in two tertiary oncological centers. We selected all consecutive women who underwent a laparoscopic or robotic staging for eEOC. Results From January 2008 to December 2016, 254 eEOC patients underwent a MIS staging (188 laparoscopic staging and 66 robotic staging). Overall, 18.1% of patients were upstaged due to pathological findings. A total of 203 (79.9%) patients received platinum-based adjuvant chemotherapy. After a median follow-up of 61 months (range 13–118), 39 (15.3%) patients experienced recurrence. The 5-years progression free survival (PFS) and overall survival rates were 84.0% and 93.8%, respectively. In the univariate analysis, favorable variables influencing PFS were young age (≤45 years), non-serous histotype, tumor grade 1-2, and FIGO stage IA/IB. In the multivariate analysis, only grade 3 was shown to keep its negative independent prognostic value (HR = 3.47; p = 0.004), whereas FIGO stage ≥ IC showed a trend toward significance (HR = 1.75; p = 0.099). Conclusion This retrospective study represents the longest follow-up of eEOC patients managed by MIS. The MIS is a valuable therapeutic option in appropriately selected patients, although a randomized controlled trial is needed.

Minimally invasive surgical staging for early stage ovarian cancer: A long-term follow up.

The objective of the present review is to thoroughly investigate the role of minimally invasive surgery (MIS) in the setting of secondary cytoreduction for ovarian cancer recurrence, comparing this approach to traditional open surgery. PubMed, ClinicalTrials.gov, Scopus and Web of Science databases (between 1st January 1989 and 1st January 2020), have been systematically queried to identify all articles reporting either laparoscopic or robotic-assisted secondary surgical cytoreduction for recurrent ovarian cancer. We also manually searched the reference lists of the identified studies. Only English language papers were considered. Two independent reviewers screened and identified the reports. A sub-analysis was performed including studies comparing MIS vs. open abdominal secondary cytoreduction. A total of 617 articles were considered. Among them, we included 12 retrospective studies on minimally invasive secondary cytoreduction, enrolling 372 patients (260 of whom were submitted to whether robotics or laparosopy). Three studies compared 69 patients who underwent MIS vs. 112 cases of open abdominal secondary cytoreduction. Other 9 articles described a total of 191 patients who had minimally invasive secondary cytoreduction for recurrent ovarian cancer without a comparative arm. The quality of the evidence was low. The decision regarding the use of MIS was left to surgeon's discretion; in general, the candidates to MIS were selected patients with single-site disease or few localizations of relapse. Compared to open surgery, MIS was associated with significantly lower blood loss, shorter hospital stay and less postoperative complications; the rate of complete cytoreduction to residual tumor =0 was 95.5% in MIS cases vs. 87.5% in laparotomy cases. The risk of complications was generally low. Disease-free and overall survival were comparable between groups. There is no consensus on the criteria to select patients for laparoscopic or robotic secondary cytoreduction. Intra-operative ultrasound has been proposed as a possible tool to better identify the site of recurrence and for confirmation of complete resection of disease. In conclusion, MIS is an option in selected patients with recurrent ovarian cancer, provided there is no widespread disease. Selection of patients appears of utmost importance to obtain satisfactory survival outcomes.

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Laparotomy vs. minimally invasive surgery for ovarian cancer recurrence: a systematic review.

The ovarian cancer recurrence occurs in 75% of patients with advanced FIGO stage, and its treatment is a challenge for the oncologist in gynecology. The standard treatment of recurrent ovarian cancer (ROC) usually includes intravenous chemotherapy according to platinum sensitivity. Furthermore, maintenance treatment with target therapies [e.g., anti-angiogenic drug or PARP inhibitors (PARPi)], should be provided if not precedently administrated. In this scenario, secondary cytoreductive surgery (SCS) remains a practical but controversial option for platinum-sensitive ROC (PSROC). So far, several retrospective series and a Cochrane meta-analysis had concluded that SCS could determine better survival outcomes in ROC with favorable prognostic characteristics, such as the presence of a single anatomical site of recurrence, or when patients are accurately selected for surgery based on complete resection's predictive models. Recently, three randomized clinical trials (RCTs) investigated the role of SCS in PSROC patients selected with different criteria. All the three RCTs showed a significant statistical advantage in progression-free survival (PFS) in the SCS group, with an even more significant difference in patients with complete cytoreduction (about 7-month PFS increased). Data on overall survival (OS) are different in the two completed trials. The GOG213 study has documented a longer OS of PSROC patients who received chemotherapy alone compared to surgery plus chemotherapy. Contrarily, the DESKTOP III trial showed 7.7 months of increased OS in the surgery group vs. chemotherapy alone, with a more difference in the complete tumor cytoreduction (CTC) group (12 months). These RCTs thereby suggest that undergoing complete cytoreduction may not be the only key and that the disease biology may also matter. Few recent retrospective series investigated the role of SCS according to BRCA mutation status and the effect of SCS in patients receiving emerging PARPi. A consequence of the developments in SCS and knowledge of different molecular pathways influencing the recurrent disease is that the future research objective should be to individualize and personalize the surgical approach.

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Update on the secondary cytoreduction in platinum-sensitive recurrent ovarian cancer: a narrative review

Background High grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet. Methods Ninety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients. Results A high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1-100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%. Conclusions A multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

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Development of a Genomic Signatures-Based Predictor of Initial Platinum-Resistance in Advanced High-Grade Serous Ovarian Cancer Patients.

Ovarian cancer (OV) has become the most lethal gynecological cancer. However, its treatment methods and staging system are far from ideal. In the present study, taking the advantage of large-scale public cohorts, we extracted a list of immune-related prognostic genes that differentially expressed in tumor and normal ovarian tissues. Importantly, an individualized immune-related gene based prognostic model (IPM) for OV patients were developed. Furthermore, we validated our IPM in Gene Expression Omnibus (GEO) repository and compared the immune landscape and pathways between high-risk and low-risk groups. The results of our study can serve as an important model to identify the immune subset of patients and has potential for use in immune therapeutic selection and patient management.

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Development of a Prognostic Model for Ovarian Cancer Patients Based on Novel Immune Microenvironment Related Genes

Objective This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. Methods This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). Results As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. Conclusions In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

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Papers

Salvage lymphadenectomy in recurrent ovarian cancer patients: Analysis of clinical outcome and BRCA1/2 gene mutational status.