Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

Objectives:To compare the survival and perioperative morbidity between primary debulking surgery(PDS) and neoadjuvant chemotherapy followed by interval debulking surgery(NAC/IDS) in treating patients with advanced epithelial ovarian cancer(EOC).Methods:We retrospectively reviewed 67 patients with stage IIIC or IV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009.Wherein,37 and 30 patients underwent PDS and NAC/IDS,respectively.Results:No difference in overall survival(OS) or progression-free survival(PFS) was observed between NAC/IDS group and PDS group(OS:41.2 vs.39.1 months,P=0.23;PFS:27.1 vs.24.3 months,P=0.37).The optimal debulking rate was 60% in the NAC/IDS group,which was significantly higher than that in the PDS group(32.4%)(P=0.024).The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion,lower nasogastric intubation rate,and earlier ambulation and recovery of intestinal function than the PDS group(P<0.05).Conclusions:NAC/IDS is less invasive than PDS,and offers the advantages regarding optimal cytoreduction rate,intraoperative blood loss,and postoperative recovery,without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC.Therefore,NAC/IDS may be a valuable treatment alternative for EOC patients.     

Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian,tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602

BackgroundWe conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.MethodsPatients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).ResultsBetween November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).ConclusionOur findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.     

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

Introduction

Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.

Patients and methods

We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.

Results

Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).

Conclusions

NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

     

Effect of tumor burden and radical surgery on survival difference between upfront,early interval or delayed cytoreductive surgery in ovarian cancer

ObjectiveWe sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0).MethodsThis retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC–IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3–4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score.ResultsFive hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score <8. Among patients with PCI ≤10, median OS after PDS was significantly higher than after early IDS or DDS. In women with PCI >10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS.ConclusionThe benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.     

Ovarian cancer

The current standard treatment for advanced ovarian cancer is primary debulking surgery (PDS) followed by postsurgical chemotherapy. We can expect a better prognosis in cases of optimal debulking (residual disease<1 cm). Unfortunately, optimal debulking in the PDS can be achieved in only about 40% of stage III/IV ovarian cancers as a rule. Neoadjuvant chemotherapy (NAC) has been recognized as an alternative treatment to primary surgical debulking for patients with apparently unresectable bulky tumors or poor performance status. Retrospective analyses revealed that overall survival was comparable between patients treated with NAC followed by interval debulking surgery (IDS) and those treated with PDS, though the former group had more advanced disease and poorer performance status.Based on these favorable results of NAC for patients with advanced disease or poor performance status, the target disease was extended to all cases of advanced disease, including patients without apparently unresectable tumors and good performance status in prospective studies. The European Organization for Research and Treatment of Cancer (EORTC) and The Japan Clinical Oncology Group (JCOG) is now conducting a phase III study comparing neoadjuvant setting treatment with standard treatment for advanced mullerian cancer, such as ovarian, tubal or peritoneal cancer. These prospective studies are expected to reveal the role of NAC for advanced müllerian cancer.     

Neoadjuvant chemotherapy,interval debulking surgery or primary surgery in ovarian carcinoma FIGO stage IV?

ObjectivesThe aim of this study was to investigate the impact of surgical approach, the extent of surgery and chemotherapy on overall survival in patients with ovarian carcinoma (OC) stage IV.MethodsWe retrospectively collected population-based data from the Norwegian Radium Hospital code registry on the diagnosis and surgery of 238 patients diagnosed with OC stage IV from 1996–2005. All patients received platinum-based chemotherapy. Surgical approach was registered as primary debulking surgery (PDS), interval debulking surgery (IDS) and delayed primary surgery (DPS). Surgery level was classified as radical surgery (RS), standard surgery (SS) or suboptimal surgery (SUBS). Univariate and multivariate analyses identified prognostic factors in PDS, IDS and DPS groups and subgroups.ResultsThere were no differences in overall survival between the PDS, IDS and DPS groups. Surgery level was significantly associated with overall survival in the whole cohort (p < 0.001), the PDS and IDS groups, but not in the DPS group. More patients with RS achieved no residual tumour (RT), but overall survival was not superior compared to no RT in the SS group. In 66 patients with no RT there were no differences in overall survival between those who underwent PDS, IDS and DPS. Chemotherapy with platinum/paclitaxel tended to improve survival. RT, World Health Organisation (WHO) performance status and histology were prognostic factors for overall survival in the whole cohort.ConclusionNo RT remains the objective, whether PDS, IDS or DPS is performed, and no differences in overall survival were found in the three treatment groups.     

Impact of surgery and chemotherapy timing on outcomes in older versus younger epithelial ovarian cancer patients: A nationwide Danish cohort study

IntroductionTo explore differences in surgical complexity, chemotherapy administration, and treatment delays between younger and older Danish patients with epithelial ovarian cancer (EOC).Materials and MethodsWe included a nationwide cohort diagnosed with EOC from 2013 to 2018. We described surgical complexity and outcomes, the extent of chemotherapy and treatment delays stratified by age (<70 and ≥ 70 years), and surgical modality (primary, interval, or no debulking surgery).ResultsIn total, we included 2946 patients. For patients with advanced-stage disease, 52% of the older patients versus 25% of the younger patients did not undergo primary debulking surgery (PDS) or interval debulking surgery (IDS). For patients undergoing PDS or IDS, older patients underwent less extensive surgery and more often had residual disease after surgery >0 cm compared to younger patients. Furthermore, older patients were less often treated with chemotherapy. Older patients had PDS later than younger. We did not find any differences between age groups concerning treatment delays. Two-year cancer-specific survival differed significantly between age groups regardless of curatively intended treatment.DiscussionThis study demonstrates that older patients are treated less actively concerning surgical and oncological treatment than younger patients, leading to worse cancer-specific survival. Older patients do not experience more treatment delays than younger ones.     

Neoadjuvant chemotherapy for ovarian cancer

The current standard treatment for advanced ovarian cancer is primary debulking surgery (PDS) followed by postsurgical chemotherapy. We can expect better prognosis in cases where optimal debulking (residual diseases<1 cm) can be achieved. Neoadjuvant chemotherapy (NAC) has been recognized as an alternative treatment to primary surgical debulking for patients with poor performance status or apparently unresectable bulky tumors. Retrospective analyses and non-randomized comparative studies revealed that overall survival was comparable between patients treated with NAC followed by interval debulking surgery (IDS) and those treated with PDS, though the former group had more advanced disease and poorer performance status. Two reports of meta-analyses of these studies revealed that the NAC setting treatment does not compromise the treatment outcome of the patients with advanced ovarian cancer. Until now, at least four phase III studies comparing NAC setting treatment with standard treatment for advanced müllerian cancer have been conducted. The results of the first study conducted by the European Organization for Research and Treatment of Cancer (EORTC) were published in 2010. They revealed a comparative outcome of NAC setting treatment with standard treatment (median survival 30 M vs 29 M) with less common surgery-related adverse effects. NAC setting treatment is now expected to become a standard treatment or one of the effective treatment options for advanced ovarian cancer in cases when other phase III studies reproduce similar results.     

间歇性肿瘤细胞减灭术与初始肿瘤细胞减灭术对晚期上皮性卵巢癌的疗效评价

目的探讨间歇性肿瘤细胞减灭术(IDS)与初始肿瘤细胞减灭术(PDS)对晚期上皮性卵巢癌(EOC)的疗效。方法根据手术方法的不同将132例晚期EOC患者分为PDS组(n=87例)和IDS组(n=45)。PDS组患者行PDS手术后接受6~8个疗程的化疗。IDS组患者行PDS手术后接受3个疗程的化疗,然后再行IDS手术后化疗3~5个疗程。观察两组患者的PDS切除范围,比较两组患者的减瘤满意率、疗效、血清CA125水平和不良反应发生情况。结果IDS组患者的PDS切除范围明显小于PDS组(P﹤0.01)。IDS组患者的减瘤满意率高于PDS组(P﹤0.05)。IDS组患者的临床疗效明显优于PDS组(P﹤0.01)。术前和第3次化疗后,两组患者的血清CA125水平比较,差异均无统计学意义(P﹥0.05)。IDS组患者PDS后的血清CA125水平高于PDS组,完成化疗后的血清CA125水平低于PDS组(P﹤0.05)。IDS组患者的不良反应总发生率低于PDS组(P﹤0.05)。结论IDS有助于提高晚期EOC患者的手术减瘤满意率和近期疗效,且不会显著增加不良反应。     

The role of changes in systemic inflammatory response markers during neoadjuvant chemotherapy in predicting suboptimal surgery in ovarian cancer

AimThe aim of this study was to investigate the possibility of using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and platelet count and their dynamic changes during chemotherapy to predict suboptimal interval debulking surgery (IDS) in stage IIIC-IVA serous ovarian cancer (OC).MethodPatients who underwent IDS after neoadjuvant chemotherapy (NAC) for stage IIIC-IVA serous OC at 3 centers between January 2008 and March 2018 were analyzed retrospectively. All women with complete blood counts both at diagnosis (T0) and after the completion of NAC but prior to IDS (T1) were included. An average of 3 weeks passed between IDS and the last cycle of NAC.ResultsA total of 214 patients were found suitable for the study. Suboptimal surgery was performed in 25.2% of the patients and optimal surgery was performed in 74.8%. The rate of change in NLR was calculated as [(NLR T0 – NLR T1)/NLR T0] × 100. A higher rate of change in NLR was found in the optimal surgery group. Recovery of thrombocytosis (When platelet count before NAC was >400,000/mm³, recovery of thrombocytosis was defined as ≤400,000/mm³ after NAC.) was found to have 85.7% sensitivity and 64.8% specificity in predicting suboptimal surgery (P < 0.001). According to both multivariate and univariate regression analysis, a large change in NLR (>17%) and recovery of thrombocytosis significantly predicted suboptimal surgery.ConclusionTo identify the likelihood of suboptimal surgery in advanced stage OC patients who undergo IDS after NAC, the dynamic change in NLR values can be examined.     

Results of interval debulking surgery in advanced stage ovarian cancer: an exposed-non-exposed study.

BACKGROUND: To study the results of interval debulking surgery (IDS) in patients treated for 'unresectable' advanced stage ovarian cancer compared with primary debulking surgery (PDS) followed by chemotherapy. PATIENTS AND METHODS: An exposed-non-exposed study including a group of 34 patients who underwent an IDS and were matched to an historic control group of 34 patients treated with PDS. RESULTS: Optimal cytoreductive surgery was achieved in 94% (32 out of 34) of patients in both groups. The rates of post-operative morbidity, blood transfusion and median length of hospitalisation were significantly reduced in the study (IDS) group, but survival did not differ in both groups. CONCLUSIONS: IDS in patients with advanced stage ovarian cancer offers the same chance of survival as PDS, but it is better tolerated.     

Days alive and out of hospital after surgical treatment of epithelial ovarian cancer: A Danish nationwide cohort study

ObjectiveDays alive and out of hospital (DAOH) is a validated outcome measure in perioperative trials integrating information on primary hospitalization, readmissions, and mortality. It is negatively associated with advanced age. However, DAOH has not been described for surgical treatment of epithelial ovarian cancer (EOC), primarily diagnosed in older patients.MethodsWe conducted a Danish nationwide cohort study including patients undergoing debulking surgery for EOC from 2013 to 2018. DAOH was explored for 30 (DAOH30), 90 (DAOH90), and 180 (DAOH180) postoperative days in younger (<70 years) and older (≥70 years) patients with advanced-stage disease stratified by surgical modality (primary (PDS) or interval debulking surgery (IDS)). We examined the associations between patient- and surgical outcomes and low or high DAOH30.ResultsOverall, 1168 patients had stage IIIC-IV disease and underwent debulking surgery. DAOH30 was 22 days [interquartile range (IQR): 18, 25] and 23 days [IQR: 18, 25] for younger and older patients treated with PDS, respectively. For IDS, DAOH30 was 25 days [IQR: 22, 26] for younger and 25 days[IQR: 21, 26] for older patients. We found no significant differences between age cohorts regarding DAOH30, DAOH90, and DAOH180. Low DAOH30 was associated with poor performance status, PDS, extensive surgery, and long duration of surgery in adjusted analysis.ConclusionsDAOH did not differ significantly between age cohorts. Surgical rather than patient-related factors were associated with low DAOH30. Our results likely reflect a high selection of fit older patients for surgery, reducing the patient-related differences between younger and older patients receiving surgical treatment.     

Preoperative Serum CA-125 Level As a Predictor for The Extent of Cytoreduction in Patients with Advanced Stage Epithelial Ovarian Cancer

BackgroundOvarian cancer is the seventh most common cancer in women worldwide and the eighth most common cause of cancer death. Due to the lack of effective early detection strategies and the unspecific onset of symptoms, it is diagnosed at an advanced stage in 75% of cases. The cancer antigen (CA) 125 is used as a prognostic marker and its level is elevated in more than 85% of women with advanced stages of epithelial ovarian cancer (EOC). The standard treatment is primary debulking surgery (PDS) followed by adjuvant chemotherapy (ACT), but the later approach is neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Several studies have been conducted to find out whether preoperative CA-125 serum levels influence treatment choice, surgical resection and survival outcome. The aim of our study was to analyse experience of single institution as Cancer comprehensive center with preoperative usefulness of CA-125.Patients and methodsAt the Institute of Oncology Ljubljana a retrospective analysis of 253 women with stage FIGO IIIC and IV ovarian cancer was conducted. Women were divided into two groups based on their primary treatment. The first group was the NACT group (215 women) and the second the PDS group (38 women). The differences in patient characteristics were compared using the Chi-square test and ANOVA and the Kaplan-Meier method was used for calculating progression-free survival (PFS) and overall survival (OS).ResultsThe median serum CA-125 level was higher in the NACT group than in the PDS group, 972 IU/ml and 499 IU/ ml, respectively. The PFS in the NACT group was 8 months (95% CI 6.4–9.5) and 18 months (95% CI 12.5–23.4) in the PDS group. The median OS was lower in the NACT group than in the PDS group, 25 months (95% CI 20.6–29.5) and 46 months (95% CI 32.9–62.1), respectively.ConclusionsPreoperative CA-125 cut off value of 500 IU/ml is a promising threshold to predict a successful PDS.Key words: ovarian cancer, tumour marker, CA-125, primary debulking surgery, neoadjuvant chemotherapy     

Prognostic impact of initial tumor load and intraperitoneal disease dissemination patterns in patients with advanced ovarian cancer undergoing complete cytoreductive surgery

IntroductionComplete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery.MethodsWe conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria.ResultsOne hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the “IDS” subgroup. In the “PDS” subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS.ConclusionInitial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.     

Phase III trial of upfront debulking surgery versus neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0602

On the basis of promising results of neoadjuvant chemotherapy (NAC) in our previous study (JCOG0206), we have been performing a Phase III study of treatment starting with NAC versus standard treatment starting with primary debulking surgery (PDS) for Stage III/IV müllerian carcinomas (ovarian, tubal and peritoneal carcinomas) since November 2006. The purposes are to prove the non-inferiority of the efficacy and to show the decrease in adverse effects resulting from reduced surgical invasiveness of treatment starting with NAC. Three hundred patients with advanced müllerian carcinomas will be randomized during 3 years. NAC arm patients undergo four cycles of NAC with paclitaxel plus carboplatin followed by interval debulking surgery and an additional four cycles of postsurgical chemotherapy. Standard arm patients undergo PDS and eight cycles of postsurgical chemotherapy with or without interval debulking surgery. The primary endpoint is overall survival. The major secondary endpoints are the incidence of adverse events and parameters representing surgical invasiveness.     

A phase 1b,open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery

AimTo evaluate the tolerability, pharmacokinetics and tumour response of first-line trebananib plus paclitaxel and carboplatin followed by trebananib maintenance in high-risk or advanced ovarian cancer.MethodsIn this open-label phase 1b study, patients received intravenous (IV) trebananib 15 mg/kg administered weekly (QW) plus paclitaxel 175 mg/m² once every 3 weeks (Q3W) and carboplatin 6 mg/mL·min Q3W followed by trebananib 15 mg/kg QW monotherapy for 18 months. End-points were dose-limiting toxicities (DLTs; primary); treatment-emergent adverse events (AEs), anti-trebananib antibodies, pharmacokinetics and tumour response (secondary).ResultsTwenty seven patients (interval debulking surgery [IDS], n = 13) were enrolled. No DLTs occurred. During the combination therapy phase, AEs (>50%) in patients with IDS were nausea, diarrhoea, fatigue, decreased appetite and thrombocytopenia. In patients with primary debulking surgery (PDS), they were nausea, diarrhoea, fatigue and localised oedema. Grade 4 AEs were neutropenia (IDS, PDS; all n = 3) and thrombocytopenia (IDS, PDS; all n = 1). No deaths occurred. Toxicity results pertaining to trebananib maintenance were immature. The treatment combination did not markedly affect the pharmacokinetics across agents. In patients with IDS (n = 14 after one patient was reassigned from PDS to IDS), 12 patients had a partial response (PR), two patients had stable disease. In patients with PDS (n = 4), three patients had a complete response, one patient had a PR.ConclusionsIn women with ovarian cancer receiving IDS or PDS, IV trebananib 15 mg/kg QW plus paclitaxel and carboplatin appears tolerable. Results suggest that the treatment combination followed by trebananib 15 mg/kg monotherapy is associated with antitumour activity.     

Total Colectomy as a Part of Ultra-Radical Surgery for Ovarian Cancer—Short- and Long-Term Outcomes

(1) Background: The aim of this study was to assess the outcomes for patients who underwent total colectomy (TC) as a part of surgery for ovarian cancer (OC). (2) Methods: We performed a retrospective analysis of 1636 OC patients. Residual disease (RD) was reported using Sugarbaker’s completeness of cytoreduction score. (3) Results: Forty-two patients underwent TC during primary debulking surgery (PDS), and four and ten patients underwent TC during the interval debulking surgery (IDS) and secondary cytoreduction, respectively. The median overall survival (mOS) in OC patients following the PDS was 45.1 months in those with CC-0 (21%) resection, 11.1 months in those with CC-1 (45%) resection and 20.0 months in those with CC-2 (33%) resection (p = 0.28). Severe adverse events were reported in 18 patients (43%). In the IDS group, two patients survived more than 2 years after IDS and one patient died after 28.6 months. In the recurrent OC group, the mOS was 6.9 months. Patient age above 65 years was associated with a shortened overall survival (OS) and the presence of adverse events. (4) Conclusions: TC as a part of ultra-radical surgery for advanced OC results in high rates of optimal debulking. However, survival benefits were observed only in patients with no macroscopic disease.     

Primary site disease and recurrence location in ovarian cancer patients undergoing primary debulking surgery vs. interval debulking surgery

IntroductionThe natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used.Material and methodsAll OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively.ResultsA total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p < 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p < 0.001), and 100% of nodal diseases had a nodal recurrence (p < 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p < 0.001) and IDS (p < 0.001) groups.ConclusionOur study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present.     

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC).MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL.ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98).ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.     

Elderly and very elderly advanced ovarian cancer patients: Does the age influence the surgical management?

Background

To examine the surgical treatment and clinical outcome of elderly and very elderly advanced epithelial ovarian cancer patients.

Methods

We retrospectively analyzed FIGO stage IIIC–IV ovarian cancer patients, divided in elderly (Group A, >65 and <75 years) and very elderly patients (Group B, ≥75 years) treated by primary debulking surgery (PDS) or by interval debulking surgery (IDS) at the Catholic University at Rome and Campobasso, Italy.

Results

164 patients were included: 123 (Group A) and 41 (Group B). Complete cytoreduction was achieved in 60 patients (60.6%) in Group A and in 20 patients (62.5%) in Group B (p = 0.75). In the remaining cases, optimal cytoreduction was performed (39 cases (39.4%) in Group A and 12 (37.5%) in Group B; p = 0.75). In Group A complete/optimal debulking was achieved in 53 patients (53.5%) at PDS and in 46 patients (46.5%) at IDS (p = 0.55). In the Group B a higher rate of patients was debulked at IDS with respect to PDS (10 (31.3%) vs. 22 patients (68.7%); p = 0.02). In Group A patients debulked at PDS showed better DFS (p = 0.007) and OS (p = 0.003) with respect to patients submitted to successful IDS, whereas in group B we did not observed any survival difference according to time of cytoreduction.

Conclusions

Our data suggest that elderly and very elderly patients may tolerate radical and ultra-radical surgery. These patients should be managed in a gynecologic oncology unit, with prudent but complete approach.