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.     

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.     

Neoadjuvant chemotherapy for advanced ovarian cancer: overview of outcomes and unanswered questions

Neoadjuvant chemotherapy for advanced ovarian cancer was initially administered as an alternative treatment for patients not suitable for primary debulking surgery (PDS) because of unresectable tumor or poor performance status. Accumulation of favorable outcomes of this treatment compared with standard treatment starting with PDS made this strategy a candidate for prospective, randomized Phase III studies without limiting the subjects to patients who were unsuitable for PDS. Among the four Phase III studies to date, the earliest study from the European Organization for Research and Treatment of Cancer (EORTC) has revealed noninferior survival with less-serious morbidity in the neoadjuvant chemotherapy arm. These data suggest that neoadjuvant chemotherapy followed by surgical cytoreduction is an acceptable management strategy for patients with advanced ovarian cancer. In this article, we review the treatment outcomes and discuss some unanswered questions, as well as possible future research in this area.     

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.     

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.     

晚期上皮性卵巢癌不同治疗方案的预后影响因素分析

目的 分析晚期上皮性卵巢癌患者接受传统治疗及新辅助化疗的预后差异,探讨影响患者预后的临床特征。方法 回顾性分析129例晚期上皮性卵巢癌患者临床资料。根据不同治疗方案分为NACT-IDS组（69例）及PDS组（60例）。结果 两组患者平均手术时间、术中出血量、手术并发症的发生率及术后住院日差异均无统计学意义（P>0.05）。NACT-IDS组及PDS组手术理想减灭率差异有统计学意义（P=0.002）。两组患者平均总生存期及无进展生存期差异均无统计学意义。根据年龄、临床分期、病理学类型等临床特征单独比较接受不同治疗方案的两组患者预后,发现差异均无统计学意义（P>0.05）。将临床特征组合进行评估时,仅接受NACT-IDS及PDS治疗并达到理想减灭的Ⅲ期患者平均总生存时间差异有统计学意义（P=0.030）。结论 对于晚期上皮性卵巢癌,建议经评估可以通过PDS达到理想减灭的Ⅲ期患者行PDS,其余晚期患者可以放宽NACT的实施标准。     

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.     

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.

     

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。     

Survival outcome and perioperative complication related to neoadjuvant chemotherapy with carboplatin and paclitaxel for advanced ovarian cancer: A systematic review and meta-analysis

ObjectiveTo compare the effectiveness and safety of neoadjuvant chemotherapy with carboplatin/paclitaxel followed by interval debulking surgery (NACT-IDS) to primary debulking surgery plus postoperative chemotherapy (PDS) for advanced ovarian cancer.MethodsA comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Ovarian Cancer Committee. Multiple public search engines including PubMed/MEDLINE and the Cochrane Database, were searched in March 2019 using the entry keywords “ovarian cancer [all fields]" AND “interval debulking surgery [all fields]”, AND “neoadjuvant chemotherapy [all fields]”. Key inclusion criteria were prospective clinical trials examining platinum-based NACT for stage II-IV epithelial ovarian cancer. The primary outcome of interest was survival, and the secondary outcome was adverse events with each intervention.ResultsAfter screening 333 studies, four phase III randomized clinical trials were identified that met the inclusion criteria. These trials included 1692 women (847 receiving NACT-IDS and 845 receiving PDS). It was found that NACT-IDS and PDS had similar overall survival (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.87–1.07, P = 0.53) and progression-free survival (HR: 0.98, 95%CI: 0.90–1.08, P = 0.74). In contrast, NACT-IDS was associated with significantly lower rates of perioperative complications (odds ratio [OR] 0.27, 95%CI: 0.20–0.36, P < 0.001) and perioperative mortality (OR: 0.17, 95%CI: 0.06–0.50, P < 0.001) compared to PDS.ConclusionThis systematic review and meta-analysis suggests that NACT-IDS with carboplatin and paclitaxel does not negatively impact the survival of women with advanced ovarian cancer compared to PDS, while perioperative complications and mortality are significantly reduced by 70–80%.     

Asian perspective on debulking surgery for advanced ovarian cancer: An E-survey

PurposeWe performed an E-survey to evaluate the practice patterns in debulking surgery for advanced ovarian cancer in Asia.MethodsWe designed a questionnaire, including 50 questions related to debulking surgery for advanced ovarian cancer. The questionnaire was sent to Gynecologic Oncologic Groups in Asia from December 2016 to February 2017.ResultsA total of 253 gynecologic oncologists from Japan (58.9%), the Republic of Korea (19%), Taiwan (12.6%), and the other counties including China (7.5%), Malaysia (0.8%), Indonesia (0.8%), and Thailand (0.4%) participated in this E-survey. The median number of debulking surgeries per year was 20, and 46.8% of the respondents preferred <1 cm as the criterion for optimal debulking surgery (ODS). The most common barrier and surgical finding precluding ODS were performance status (74.3%) and disease involving the porta hepatis (71.5%). Moreover, 63.2% had a fellowship program, and only 15% or less had opportunities to receive additional training courses in general, thoracic, or urologic surgery. The median percentage of patients receiving neoadjuvant chemotherapy (NAC) was 30%, and the achieved rate of ODS in primary debulking surgery (PDS) and interval debulking surgery (IDS) was 65% and 80%, respectively. Most of the respondents required three to 6 h for PDS (48.6%) and IDS (58.9%). Moreover, more than 50% depended on ultra-radical surgery conducted by specialists.ConclusionsThe ODS criteria are relatively lenient with a preference for NAC in 30% of the respondents in Asia. This trend might be associated with the dependence on aggressive surgery performed by specialists.     

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     

Primary surgery or neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer

Advanced ovarian cancer has a poor prognosis. De-bulking surgery and platinum-based chemotherapy are the cornerstones of the treatment. Primary debulking surgery has been the standard of care in advanced ovarian cancer. Recently a new strategy with neoadjuvant chemotherapy followed by interval debulking surgery has been developed. In a recently published randomised trial of the EORTC-NCIC (European Organisation for Research and Treatment of Cancer - National Cancer Institute Canada) in patients with extensive stage IIIc and IV ovarian cancer it was shown that the survival was similar for patients randomised to neoadjuvant chemotherapy followed by interval debulking compared to primary debulking surgery, followed by chemotherapy. The post-operative complications and mortality rates were lower after interval debulking than after primary debulking surgery. The most important independent prognostic factor for overall survival was no residual tumour after primary or interval debulking surgery. In some patients obtaining the goal of no residual tumour at interval debulking is difficult due to chemotherapy-induced fibrosis. On the other hand the patients randomised had very extensive stage IIIc and IV disease and in patients with metastases smaller than 5 cm the survival tended to be better after primary debulking surgery. Hence, selection of the correct patients with stage IIIc or IV ovarian cancer for primary debulking or neoadjuvant chemotherapy followed by interval debulking surgery is important. Besides imaging with CT, diffusion MRI and/or PET-CT, also laparoscopy can play an important role in the selection of patients. It should be emphasised that the group of patients included in this study had extensive stage IIIc or IV disease. Surgical skills, especially in the upper abdomen, remain pivotal in the treatment of advanced ovarian cancer. However, very aggressive surgery should be tailored according to the general condition and extent of the disease of the patients. Otherwise, this type of aggressive surgery will result in unnecessary postoperative morbidity and mortality without improving survival. Hence, neoadjuvant chemotherapy should not be an easy way out, but is in some patients with stage IIIc or IV ovarian cancer a better alternative treatment option than primary debulking. According to the current treatment algorithm at the University Hospitals Leuven about 50% of the patients with stage IIIc or IV ovarian cancer are selected for neoadjuvant chemotherapy.     

The role of neoadjuvant chemotherapy in the treatment of advanced ovarian cancer

Primary cytoreductive surgery followed by chemotherapy represents the current standard treatment for patients with advanced ovarian cancer. Neoadjuvant chemotherapy followed by interval debulking surgery has been proposed as an alternative approach for the initial management of bulky ovarian cancer, aiming at the improvement of surgical efficiency and patients' quality of life. According to the hitherto published studies, consisting mainly of retrospective observations, neoadjuvant chemotherapy followed by interval cytoreduction appears to improve the prognosis and quality of life in selected groups of patients. The survival outcome in these patients is similar to that of the conventional approach, or even better in some of the cases. Moreover, patients undergoing debulking surgery after having received neoadjuvant chemotherapy had a reduced perioperative morbidity compared to patients undergoing primary cytoreduction. Concurrently, neoadjuvant chemotherapy provides preoperative knowledge of tumor chemosensitivity, hence allowing the surgeon to choose appropriately aggressive treatment. However, until the results of prospective randomized trials become available, neoadjuvant chemotherapy followed by interval surgery should be applied only to individual cases and primarily in the context of clinical trials.     

The role of neoadjuvant chemotherapy in ovarian cancer

Introduction: Ovarian cancer is mostly diagnosed at advanced stage. Better survival is achieved through complete debulking surgery and chemotherapy. Historically, neoadjuvant chemotherapy (NAC) has been introduced for unresectable disease to decrease tumor load and perform a unique complete surgery. Four randomized control trials have compared primary debulking surgery to NAC, but there is still controversy about the use of neoadjuvant chemotherapy and questions about its modalities.

Areas covered: We made a review of knowledge on benefits of NAC compared to primary debulking chemotherapy, in terms of survival and morbidity, methods of administration, new drugs in early and late phase trials, the selection of patients. Similar survival was observed after NAC and interval debulking surgery or primary debulking surgery. Morbidity of surgery was decreased after interval debulking compared primary debulking surgery. Conventional drugs are carboplatin and paclitaxel. Safety of bevacizumab was evaluated in phase 2 trials associated with conventional drugs. Immunotherapy trials are enrolling patients in phase 1 study.

Expert commentary: NAC followed by debulking surgery is the best treatment for patients with advanced ovarian cancer.     

Strategies for marginally resectable tumor in patients with advanced ovarian cancer

There are approximately 7, 000 cases of ovarian cancer in Japan every year. The lack of an appropriate examination for ovarian cancer contributes to nearly half the cases being undetected until reaching advanced stages III and IV. By the ovarian cancer treatment guidelines, primary debulking surgery is a standard modality for the initial treatment of ovarian cancer. Many studies have reported that the prognosis is clearly improved once optimal surgery(residual disease<1 cm)is successfully performed for advanced ovarian cancer. Actually, no residual disease group that underwent complete cytoreductive surgery was improved more significantly than the residual disease<1 cm group. For achievement of a complete cytoreductive surgery, there is a need to devise some appropriate strategies for marginally resectable tumors in patients with advanced ovarian cancer.     

不同治疗方式对卵巢上皮癌患者铂类药物耐药性的影响

目的 本研究回顾性分析比较初始肿瘤细胞减灭术（primary debulking surgery, PDS）辅以铂类药物的联合化疗和新辅助化疗后行间隔肿瘤细胞减灭术（neoadjuvant chemotherapy-intervaldebulking surgery, NACT-IDS）两种治疗方式对卵巢上皮癌患者铂类药物耐药性的影响。 方法 选择2007年1月至2013年12月符合研究要求的上皮性卵巢,输卵管和腹膜癌Ⅲ、Ⅳ期患者共87例,分为PDS（n=56）组和NACT-IDS（n=31）组,比较两组对铂类药物的敏感度,单因素及多因素Logistic回归分析各项基线资料与铂类药物耐药性的关系。 结果 以铂类药物为基础的初次治疗后,NACT-IDS组4例（7.1%）为铂耐药,PDS组也有4例（12.7%）,耐药率比较两组差异有统计学意义（P<0.05）。采用多因素Logistic回归控制分析独立相关因素,NACT-IDS将增加产生铂类药物耐药的风险。手术残余病灶大小和临床分期仍是影响复发时间和铂耐药率的显著相关因素。 结论 晚期上皮性卵巢癌患者采取NACT-IDS治疗方式,与PDS治疗方式相比,有效化疗反应率相当,但更易出现铂类药物耐药。     

晚期上皮性卵巢癌术前新辅助化疗的临床总结

探讨晚期卵巢癌能否行手术治疗的预测因素及新辅助化疗在晚期卵巢癌中的临床价值。方法:回顾性分析了大连医科大学附属第一医院1996年1月至2008年12月收治的Ⅲ～Ⅳ期晚期卵巢癌病例92例,其中18例接受新辅助化疗（NAC组）,74例接受初次手术（PCS组）。结果:使初次肿瘤细胞减灭术满意率降低的因素:伴有合并症（P=0.022）;初次治疗时存在胸腔积液（P=0.011）;CA125>1 000 U/L（P=0.030）;有肝、肺转移的Ⅳ期患者（P=0.031）。新辅助化疗的总有效率为66.7%。新辅助化疗可以提高肿瘤细胞减灭术的满意率（P=0.022）,缩短引流管置留天数（P=0.011）,减少腹水量（P=0.005）、术中出血量（P=0.048）,但在手术时间、输血量、平均住院天数、患者生存时间方面,NAC组与PCS组的差异无统计学意义（P>0.05）。结论:伴有合并症、胸腔积液、CA125>1 000 U/L、临床分期为Ⅳ期、表现为肝、肺转移的患者适合新辅助化疗。新辅助化疗可以提高肿瘤细胞减灭术的满意率,减少术中、术后并发症,可能会改善患者预后。      

Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

     

Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials.

The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor.