Ovarian cancer (OC) remains a fatal malignancy because most patients experience recurrent disease, which is resistant to chemotherapy. The outcomes for patients with platinum-resistant OC are poor, ...response rates to further chemotherapy are low and median survival is lower than 12 months. The complexity of platinum-resistant OC, which comprises a heterogeneous spectrum of diseases, is indeed far from being completely understood. Therefore, comprehending tumors’ biological behaviour to identify reliable biomarkers, which may predict responses to therapies, is a demanding challenge to improve OC management. In the age of precision medicine, efforts to overcome platinum resistance in OC represent a dynamic and vast field in which innovative drugs and clinical trials rapidly develop. This review will present the exceptional biochemical environment implicated in OC and highlights mechanisms of chemoresistance. Furthermore, innovative molecules and new therapeutic opportunities are presented, along with currently available therapies and ongoing clinical trials.
Abstract Background In the last decades, several efforts have been done to clarify the role of BRCA mutational status in women with advanced ovarian cancer demonstrating its role in cancer ...development, as well as the prognostic significance of BRCA genotype. Objctive Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients. Study Design this is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with FIGO Stage IIIC-IV disease, at least 18 months of follow-up time, tested for BRCA 1/2 germline mutation status. Disease presentation was analyzed using the following variables: laparoscopic predictive-index value, incidence of bulky lymph nodes and ovarian masses. Progression-free survival was defined as the months elapsed from initial diagnosis (staging laparoscopy) and recurrent disease or last follow-up. Results 324 high-grade serous ovarian cancer patients received BRCA testing, and 273 fulfilled inclusion criteria. BRCA1/2 germline mutations were observed in 107 women (39.2%). No differences were documented according to BRCA mutation status in terms of FIGO Stage, CA125 levels, and presence of ascites. In patients with BRCA1/2 mutations we observed a higher incidence of peritoneal spread without ovarian mass (25.2% versus 13.9%; p-value=0.018), and of bulky lymph nodes (30.8% versus 17.5%, p-value=0.010) compared with women showing BRCA1/2 wild type genotype. Furthermore, women with BRCA1/2 mutations showed high peritoneal tumor load (laparoscopic predictive-index value≥8; 42.1% versus 27.1%; p-value=0.016) more frequently. Focusing on survival, no differences in term of median progression-free survival were observed among women treated with primary debulking surgery and neoadjuvant chemotherapy in the group of patients with BRCA1/2 mutations (p-value=0.268). On the other hand, in women showing BRCA wild type genotype, median progression-free survival after primary debulking surgery was 8 months longer compared with patients treated with neoadjuvant chemotherapy approach (26 months versus 18 months; p-value=0.003). Conclusions women with BRCA1/2 mutations show at diagnosis higher peritoneal tumor load, and increased frequency of bulky lymph nodes compared to patients without germline BRCA mutations. Primary debulking surgery seems to ensure a longer progression-free survival in women with BRCA wild type genotype compared to neoadjuvant chemotherapy. BRCA testing might be a reliable tool to personalize treatment in patients with high-grade serous ovarian cancer, thus giving novel points of discussion to the ongoing debate regarding the best initial treatment approach.
Purpose
The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma.
Methods
This ...multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case–control matching was used to adjust the baseline characteristics.
Results
A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (
p
= 0.542 and
p
= 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (
p
< 0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively;
p
= 0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively;
p
= 0.114) or recurrence pattern (
p
= 0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (
p
= 0.011 and
p
= 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (
p
= 0.020).
Conclusions
Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.
Background
Recently, it was reported that minimally invasive surgery (MIS) has a negative impact on early-stage cervical cancer (ECC) patient survival. At the same time, advantages of MIS regarding ...quality of life and low rate of intra- and postoperative complications are well known. Therefore, it is essential to select patients who may benefit from MIS without worsening their oncologic outcomes. The aim of this study is to investigate which pathological factors could guide surgeons’ choice about the best approach in ECC.
Patients and Methods
Patients with 2009 FIGO stage from IA1 with lymphovascular space invasion (LVSI) to IB1/IIA1 treated by open or laparoscopic surgery were judged eligible for the study. Disease-free survivals (DFS) of both approaches were tested in subgroups, defined according to histology, tumor size, grading, LVSI, parametrial involvement, and nodal status.
Results
A total of 423 patients were enrolled (217 in the open and 206 in the laparoscopic group). No difference between open surgery and laparoscopy was found among subgroups defined according to histology, grading, LVSI, parametrial involvement, or nodal status. Among patients with tumor > 20 mm, laparoscopy showed a significantly higher relapse risk hazard ratio (HR): 2.103,
p
= 0.030. Among patients with tumor
<
20 mm, laparoscopy showed DFS superimposable to open surgery (HR: 0.560,
p
= 0.128).
Conclusions
Tumor size of 20 mm appeared as the only independent discrimination criterion in patients whose prognosis is affected by surgical approaches.
Systematic paraaortic and bilateral pelvic lymphadenectomy is the standard of a comprehensive surgical staging in presumed early epithelial ovarian cancer, but no prospective randomized evidence ...suggests a possible therapeutic value. Moreover, this procedure is associated with potential severe morbidity. The Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial is a prospective study designed to test whether sentinel node detection can accurately predict nodal status in a cohort of women with early epithelial ovarian cancer.
We here present the results of the first part of the Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial, regarding the feasibility of the sentinel lymph node technique and the preliminary findings regarding its safety and accuracy.
The Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial is a prospective, phase II, single-arm study included patients with presumed stages I–II epithelial ovarian cancer planned for immediate or delayed minimally invasive comprehensive staging. The ovarian pedicle is injected with 2 mL of a 1.25 mg/mL indocyanine green solution. The pelvic and lumboaortic retroperitoneum is then accessed and inspected to identify and remove sentinel nodes. After sentinel node procedure, staging is completed including systematic pelvic and paraaortic lymphadenectomy. Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (ie, the maximum marginal error) d = 5%, a type I error α = 0.05, a sample size of 160 patients is needed to test the general hypothesis. Here we present the preliminary results on the first 31 patients enrolled.
Thirty-one patients were included. Sentinel node was identified in 21 patients (detection rate, 67.7%). The detection rate was significantly higher in women undergoing immediate vs delayed staging (88.9% vs 41.7%, P = .003). Four patients had positive nodes. In all the patients with lymphatic dissemination, a positive sentinel node was identified (sensitivity, 100%; false-negative rate, 0%; negative predictive value, 100%). One (3.2%) intra- and 2 (6.5%) postoperative grade I complications occurred.
Our data show that the detection of sentinel node in early epithelial ovarian cancer is low when patients are submitted to delayed-staging surgery. However, sentinel node procedure is feasible and has the potential to provide reliable and useful information on nodal status and may allow the avoidance of systematic lymphadenectomy in the majority of patients.
Background
Phase 3 randomized clinical trials have been designed to compare secondary cytoreductive surgery followed by systemic therapy with systemic therapy alone for management of patients with ...recurrent ovarian cancer. This study aimed to compare differences in clinical outcomes between these two treatment approaches.
Methods
The PRISMA statement was applied. Only phase 3 randomized clinical trials were included in the final analysis.
Results
Three randomized clinical trials (
n
= 1250 patients) were identified. Secondary cytoreductive surgery was associated with significantly better progression-free survival (PFS) improvement than systemic therapy alone (hazard ratio HR, 95% CI, 0.61–0.78;
p
< 0.001). The PFS benefit was greater for the complete resection subpopulation (HR, 0.56; 95% CI, 0.48–0.66;
p
< 0.001). The HR of overall survival (OS) was similar between the groups (HR, 0.93; 95% CI, 0.78–1.10;
p
= 0.37), but it was 0.73 (95% CI, 0.59–0.91) in favor of the complete resection subpopulation.
Conclusion
This meta-analysis showed secondary cytoreductive surgery as superior to systemic therapy alone in terms of PFS. The PFS and OS benefits were particularly observed for complete surgical resection. The impact on OS in the general population remains to be proven.
Purpose
Reporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer.
Methods
The ...records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico “Agostino Gemelli” IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated.
Results
Fifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (
p
= 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20 months and 13 months, respectively (
p
= 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18 months for vaginectomy and PE, respectively (
p
= 0.161).
Conclusions
The vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.
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